Contents ABVD

Appendix B Chemotherapy Regimens

Contents ABVD ...... 1 ALL – Dana Farber ...... 2 ATG & Cyclosporin...... 3 Bortezomib (Velcade®) ...... 4 CBV...... 5 Chlorambucil...... 6 Chlorambucil + Rituximab ...... 7 CHOMP ...... 8 CHOP...... 10 CHOP + Rituximab ...... 11 Cladribine (2-CDA) ...... 12 CVP (IV) ...... 13 CVP (IV) + Rituximab ...... 14 CVP (Oral) ...... 15 CVP (Oral) + Rituximab...... 16 DHAP...... 17 DPACE...... 19 ESHAP...... 20 FCM ...... 22 FCM + Rituximab...... 23 Fludarabine ...... 24 Fludarabine + Rituximab...... 25 GDP ...... 26 HDMVP ...... 27 HIDAC Consolidation ...... 29 Hyper-CVAD ...... 31 Intravenous Immunoglobulin...... 35 IV Iron Replacement (Venofer®)...... 36 Lenalidomide ...... 37 Magrath ...... 38 Melphalan + Prednisone...... 44 MPT ...... 45 MPV ...... 46 Mini-BEAM ...... 47 MOPP ...... 49 NOVE...... 50 NOVE-HIDAC ...... 51 POMP Maintenance ...... 52 Rituximab...... 53 Thalidomide/Dexamethasone ...... 54 Vidaza ...... 55 VP-16/Melphalan ...... 56 VP-16/Prednisone ...... 59 7+3 Induction...... 60

Appendix B

ABVD

Indications First-line therapy for Hodgkin's lymphoma

Drug Regimen Doxorubicin 25 mg/m2 by slow IV push days 1 and 15 Bleomycin 10 U/m2 by slow IV push days 1 and 15 Vinblastine 6 mg/m2 by quick IV push days 1 and 15 Dacarbazine 375 mg/m2 in 500 mL NS over 75 minutes days 1 and 15

Cycle Frequency Repeat every 28 days (for a total of 4-8 cycles)

Dose Hematologic Toxicity Modification Hold dose for 1 week if absolute neutrophil count < 1.0 x 109/L or platelets < 75 x Criteria 109/L

Filgrastim support should be considered after first episode of febrile neutropenia or dose delay ≥ 1 week

Renal Failure If creatinine clearance = 0.2 – 1.0 mL/second, reduce bleomycin to 75% dose If creatinine clearance < 0.2 mL/second, reduce bleomycin to 50% dose

Hepatic Dysfunction If bilirubin = 26-51 μmol/L or AST = 60-180 IU/L, reduce doxorubicin to 75% dose and vinblastine to 50% dose

If bilirubin = 52-85 μmol/L or AST > 180 IU/L, reduce doxorubicin to 50% dose and vinblastine to 25% dose

If bilirubin > 85 μmol/L, omit doxorubicin and vinblastine

Cost $355 per 28-day cycle

References Bonadonna, G. and A. Santoro, ABVD chemotherapy in the treatment of Hodgkin's disease. Cancer Treat Rev, 1982. 9(1): p. 21-35.

Abbreviations: IV = intravenous; NS = normal saline

Appendix B Page 1 of 61

ALL – Dana Farber

Indications First-line therapy for ALL

Drug Regimen i. Induction (x 1 cycle) Prednisone 10 mg/m2 q.i.d. p.o. days 1- 28 Vincristine 2 mg IV in 50 mL NS over 15 minutes days 1, 8, 15, 22 Doxorubicin 30 mg/m2 IV push days 1 and 2 Methotrexate 4000 mg/m2 IV in 1 L NS over 4 hours day 3 Leucovorin 200 mg/m2 IV 36 hours post MTX and 24 mg/m2 q6h IV or p.o. until MTX level < 0.1 μmol/L L-Asparaginase 25 000 IU/m2 IM day 5 MTX+ ARA-C MTX 12 mg + ARA-C 40 mg IT in preservative-free NS (total 5 mL) days 1, 15, 28 Allopurinol + 300 mg p.o. daily and Cotrimoxazole 1 DS tablet p.o. b.i.d. q MWF (Septra®)

ii. CNS Therapy (x 1 cycle) Vincristine 2 mg IV in 50 mL NS over 15 minutes day 1 6-Mercaptopurine 50 mg/m2/day p.o. q.h.s. x 14 days (round off dose to nearest 50 mg) Doxorubicin 30 mg/m2 IV day 1 push MTX + ARA-C MTX 12 mg + ARA-C 40 mg IT in preservative-free NS (total 5 mL) days 1, 4, 8, 11 Cranial Irradiation 1800 cGy over 10 fractions days 1-10

iii. Intensification (3-week cycle x 10 cycles) Vincristine 2 mg IV in 50 mL NS over 15 minutes day 1 of each cycle Dexamethasone 18 mg/m2/day p.o. (in 2 divided doses) days 1-5 of each cycle 6-Mercaptopurine 50 mg/m2/day p.o. q.h.s. days 1-14 of each cycle (round off dose to nearest 50 mg) Doxorubicin 30 mg/m2 IV push day 1 (to maximum of 300 mg/m2 cumulative dose [i.e. 7th cycle]) Methotrexate 30 mg/m2 in 250 mL NS over 1 hour or IM days 1, 8, 15 L-Asparaginase 12 500 IU/m2 weekly x 30 weeks – IM MTX + ARA-C MTX 12 mg + ARA-C 40 mg IT in preservative-free NS (total 5 mL) every 18 weeks

iv. Continuation (3-week cycle until 2 years after CR) Vincristine 2 mg IV in 50 mL NS over 15 minutes day 1 (each cycle) Dexamethasone 6 mg/m2/day p.o./IV (in two divided doses) days 1-5 (each cycle) 6-Mercaptopurine 50 mg/m2/day p.o. q.h.s. days 1-15 (each cycle) Methotrexate 30 mg/m2 IV in 250 mL NS over 1 hour or IM weekly MTX + ARA-C MTX 12 mg + ARA-C 40 mg IT in preservative-free NS (total 5 mL) every 18 weeks

References Silverman, L.B., et al., Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01. Blood, 2001. 97(5): p. 1211-8. Protocol has been modified according to the NCIC AL.4 Protocol 2007

Abbreviations: ALL = acute lymphocytic leukemia; ARA-C = cytarabine; CR = complete response; IT = intrathecally; IV = intravenously; MTX = methotrexate; p.o. = by mouth; q.i.d. = four times daily; q.h.s. = at bedtime

Page 2 of 61 Appendix B

ATG & Cyclosporin

Indications First-line immunotherapy for aplastic anemia

Drug Regimen ATG (first-line) Horse ATG (ATGM® - Upjohn) Test Dose Horse ATG 25 mg (o.5 mL) in 100 mL normal saline infused intravenously over 1 hour monitoring for allergic reaction Treatment Dose 40 mg/kg/day IV days 1-4

ATG (second-line) or if allergic to horse ATG Rabbit ATG (Thymoglobulin® - SangStat) Test Dose Rabbit ATG (Thymoglobulin® - SangStat) 2.5 mg (0.5 mL) in 100 mL normal saline infused intravenously over 1 hour monitoring for allergic reaction Treatment Dose 3.75 mg/kg/day IV days 1-5

Premedication – Daily 1 hour prior to each dose Prednisone 1 mg/kg p.o. Diphenhydramine (Benadryl®) 50 mg IV Acetaminophen (Tylenol®) 1000 mg p.o.

Cyclosporin 5 mg/kg/day day 14 onwards Cyclosporin dose should be adjusted to achieve a trough level of 200-400 μg/L Patients > 60 years trough level 150-250 μg/L Children trough level of 100-150 μg/L

Note: Monitor renal function, blood pressure, magnesium

Cyclosporin can be tapered after 6 months of therapy if counts have normalized and have been stable for 1-2 months

Serum Sickness Prophylaxis Prednisone 1 mg/kg/day to be continued for 9 days after completion of ATG, then tapered over next 5 days

Cycle Frequency One course is given routinely

A second course of ATG may be administered if there has been no response by 3 months post treatment, or at later relapse

Patients may become sensitized to horse ATG after one administration and thus are at risk of anaphylaxis. Patients receiving a second course of ATG, or patients that demonstrate an allergic reaction to the test dose of horse ATG should be given the rabbit ATG formulation

Cost 1 course ATG = $13 000 and approximate costs for cyclosporin for 6 months = $4500

References Marsh, J.C., et al., Guidelines for the diagnosis and management of acquired aplastic anaemia. Br J Haematol, 2003. 123(5): p. 782-801. Rosenfeld, S., et al., Antithymocyte globulin and cyclosporine for severe aplastic anemia: association between hematologic response and long-term outcome. Jama, 2003. 289(9): p. 1130-5.

Abbreviations: ATG = antithymocyte globulin; IV = intravenously; p.o. = by mouth

Appendix B Page 3 of 61

PHYSICIAN’S ORDERS

PHYSICIAN’S ORDERS All orders shall be DATED, TIMED, and SIGNED All medication orders shall be written in the GENERIC or non-proprietary name. All orders shall be written legibly using ball point pen. PATIENT IDENTIFICATION

Signature TIME of & nurse DATE

YYYY/MM/DD

HORSE Antithymocyte Globulin (ATG, Atgam®) Orders for Aplastic Anemia Yes No Doctor must check off appropriate orders. There are two Antithymocyte Globulin Order Forms (horse and rabbit). I have selected the appropriate order form for this patient. Doctor’s Signature:______PRINT NAME:______Admit to Dr.______on ______(YYYY/MM/DD) Diagnosis______Infuse ATG by central line (see Note #1 on back of this page). Pre-chemotherapy Bloodwork: (if not done within one week prior to admission) CBC, differential, electrolytes, blood glucose, calcium profile, liver profile, renal profile, LDH, uric acid Hold ATG until physician writes an order on the Doctor’s Order Form to proceed with ATG test Dose Monday, Wednesday and Friday – CBC, renal profile, calcium profile, liver profile, group and screen cyclosporine (CSA) trough levels 1h prior to first dose of day, starting Day 15 (_____/____/____) (YYYY/MM/DD) and every Monday and Friday, thereafter. Target CSA level = 200-300 mcg/L Daily weight (kg) before breakfast Record intake and output daily Diet:______Monitoring during ATG infusions (See Note #2 on back of this page) Day 1: • Vital signs prior to infusion, then q 15 min x 1 h, q 30 min x 1 h, then q 1 h until infusion is completed • Monitor for allergic reactions continuously during the first 15 minutes and then q 1 h until infusion completed: fever (temperature ≥ 38°C), chills, hives, rash, pruritus, SBP change (increase or decrease of ≥ 20% from pre-infusion reading), shortness of breath, and chest pain. • Stop infusion and notify MD if reaction(s) observed Days 2-4: • Vital signs q 30 min x 1 h, then q 2 h until infusion is completed • Monitor for allergic reactions (see Day 1) every four hours. • Stop infusion and notify MD if reaction(s) observed

Doctor’s Signature: PRINT NAME: Pager: DISTRIBUTION: White Original - Chart Yellow Copy - Pharmacy Page 1 of 3

PR 10034 (2008/12/07) NOTES:

1. Ensure that patient has central venous catheter (CVC) access. To avoid delay in therapy infuse ATG through a peripheral line only if central venous access is not feasible/available. 2. If patient experienced an allergic reaction or abnormal vital signs (temperature ≥ 38°C, SBP increase or decrease of ≥ 20% from pre-infusion reading) during the previous day’s infusion, consider extending the infusion rate to 12 hours and/or more frequent monitoring (write orders on a Physician’s Order Form). 3. Serum sickness manifesting as fever, arthralgia, lymphadenopathy and cutaneous eruptions (morbilliform rash) occurs in the majority of patients with aplastic anemia treated with ATG. Symptoms generally develop within 7 to 14 days after initiating ATG. Prescribe hydrocortisone sodium succinate (Solu-Cortef®) 100 mg q6h. 4. Prednisone taper. Consider graduated taper over 5 days, starting on day 14. Write tapering orders on a Physician’s Order Form.

Horse ATG Infusion Dose (40 mg/kg/day) Patient Prednisone Cyclosporine Weight Day 1 Dose Dose for Days (1 mg/kg/day) (2.5 mg/kg) (kg) (25 mg Test 2-4 Rounded to 5 mg Rounded to 25 mg Dose has been (Rounded to subtracted) (mg) 250 mg) 45 1725 1750 45 100 46 1725 1750 45 125 47 1975 2000 45 125 48-52 1975 2000 50 125 53 1975 2000 55 125 54 2225 2250 55 125 55-57 2225 2250 55 150 58-59 2225 2250 60 150 60-63 2475 2500 60 150 64-65 2475 2500 65 150 66-68 2725 2750 65 175 69-71 2725 2750 70 175 72 2975 3000 70 175 73-74 2975 3000 75 175 75-77 2975 3000 75 200 78 2975 3000 80 200 79-82 3225 3250 80 200 83-84 3225 3250 85 200 85 3475 3500 85 200 86-87 3475 3500 85 225 88-90 3475 3500 90 225 91-92 3725 3750 90 225 93-94 3725 3750 95 225 95-96 3725 3750 95 250 97 3975 4000 95 250 98-100 3975 4000 100 250

PR 10034 (2008/12/07) PHYSICIAN’S ORDERS

Signature TIME of & nurse DATE

YYYY/MM/DD

HORSE Antithymocyte Globulin (ATG, Atgam®) Orders for Aplastic Anemia Yes No Doctor must check off appropriate orders. Have the following medication readily available in the patient’s medication bin: epinephrine 1:1,000 inj methylprednisolone (Solu-Medrol®), 125mg diphenhydramine (Benadryl®) Inj, 50mg salbutamol inhaler + spacer device Monitor for signs or symptoms of serum sickness (see Note #3 on back of this page). Notify MD if signs or symptoms of serum sickness develop. Height:______cm Weight:______kg BSA______m2 Day 1: TEST DOSE _____/_____/_____(YYYY/MM/DD) Pre-medication NOT to be given PRIOR to test dose Horse ATG (Atgam ®) 0.5mL (25mg) in 100mL of Normal Saline IV to run over 1 hour through 0.2-micron in-line filter. Vital Signs prior to test dose infusion, then q 15 min x 1 hour. Monitor for allergic reactions: fever (temperature ≥ 38°C), chills, hives, rash, pruritus, hyper- or hypotension (SBP increase or decrease of ≥ 20% from pre-infusion reading), shortness of breath, and chest pain continually during the first 15 minutes, then q15 min until infusion completed. If reaction(s) observed stop infusion and notify MD. If no allergic reaction within 1 hour of starting Test Dose proceed with Day 1 infusion Days 1-4: PRE MEDICATION (Begin only if patient tolerates ATG Test Dose) prednisone 1mg/kg/day rounded to nearest 5mg (=_____mg-see back of this page for rounded dose) po, 60 minutes prior to first dose (Day 1) of ATG, then daily x 3 days 60 minutes prior to each subsequent ATG dose (total = 4 doses). acetaminophen 1000 mg po, 60 minutes prior to first dose (Day 1) ofATG, then daily x 3 days 60 minutes prior to each subsequent ATG dose (total = 4 doses). diphenhydramine (Benadryl®) 50 mg IV, 60 minutes prior to first dose (Day 1) of ATG, then daily x 3 days 60 minutes prior to each subsequent ATG dose (total = 4 doses).

Doctor’s Signature: PRINT NAME: Pager: DISTRIBUTION: White Original - Chart Yellow Copy - Pharmacy Page 2 of 3

PR 10034 (2008/12/07) NOTES:

PR 10034 (2008/12/07) PHYSICIAN’S ORDERS

Signature TIME of & nurse DATE

YYYY/MM/DD

HORSE Antithymocyte Globulin (ATG, Atgam®) Orders for Aplastic Anemia Yes No Doctor must check off appropriate orders. PRN Medications diphenhydramine (Benadryl®) 50mg IV q 4h prn for rash acetaminophen 500-1000 mg po q 4 h prn for temperature ≥ 38ºC (total of scheduled and prn doses must not exceed 4,000 mg daily) Day 1: ATG INFUSION _____/_____/_____(YYYY/MM/DD) Horse ATG 40mg/kg (=______mg-see back of this page: “Day 1 Infusion Dose”) in 1000 mL of Normal Saline to IV run over 12 hours through a 0.2-micron in-line filter. Day 2: ATG INFUSION _____/_____/_____(YYYY/MM/DD) If no allergic reactions observed with Day 1 infusion, administer horse ATG 40mg/kg rounded to nearest 250mg (=______mg -see back of this page “Infusion for Days 2-4”) in 1000 mL of Normal Saline IV to run over 6 hours through a 0.2-micron in-line filter. If reaction(s) observed with Day 1 infusion, increase infusion rate to 12 hours (see Note #2 on back of this page). Day 3: ATG INFUSION _____/_____/_____(YYYY/MM/DD) If no allergic reactions observed with Day 2 infusion administer horse ATG 40mg/ kg rounded to nearest 250mg (=______mg -see back of this page “Infusion for Days 2-4”) in 1000 mL of Normal Saline IV to run over 6 hours through a 0.2-micron in-line filter. If reaction(s) observed with Day 2 infusion, increase infusion rate to 12 hours (see Note #2 on back of this page). Day 4: ATG INFUSION _____/_____/_____(YYYY/MM/DD) If no allergic reactions observed with Day 3 infusion administer horse ATG 40 mg/kg rounded to nearest 250mg (=______mg –see back of this page “Infusion for Days 2-4”) in 1000 mL of Normal Saline IV to run over 6 hours through a 0.2-micron in-line filter. If reaction(s) observed with Day 3 infusion, increase infusion rate to 12 hours (see Note #2 on back of this page). Day 5: _____/_____/_____(YYYY/MM/DD) prednisone 1mg/kg rounded to nearest 5mg (= _____ mg-see back of this page for rounded dose) po daily with breakfast x 9 days Day 14: _____/_____/_____(YYYY/MM/DD) Contact physician regarding tapering of prednisone dose (see Note #4 on back of this page). cyclosporine 2.5mg/kg rounded to nearest 25mg (= ______mg - see back of this page for rounded dose) po BID for a minimum duration of 6 months

Doctor’s Signature: PRINT NAME: Pager: DISTRIBUTION: White Original - Chart Yellow Copy - Pharmacy Page 3 of 3

PR 10034 (2008/12/07) NOTES:

PR 10034 (2008/12/07) PHYSICIAN’S ORDERS

Signature TIME of & nurse DATE

YYYY/MM/DD

RABBIT Antithymocyte Globulin (ATG, Thymoglobulin®) Orders for Aplastic Anemia Yes No Doctor must check off appropriate orders. There are two Antithymocyte Globulin Order Forms (horse and rabbit). I have selected the appropriate order form for this patient. Doctor’s Signature:______PRINT NAME:______Admit to Dr.______on ______(YYYY/MM/DD) Diagnosis______Infuse ATG by central line (see Note #1 on back of this page) Pre-chemotherapy Bloodwork: (if not done within one week prior to admission) CBC, differential, electrolytes, blood glucose, calcium profile, liver profile, renal profile, LDH, uric acid Hold ATG until physician writes an order on the Doctor’s Order Form to proceed with ATG Test Dose Monday, Wednesday and Friday – CBC, renal profile, calcium profile, liver profile, group and screen cyclosporine (CSA) trough levels 1h prior to first dose of day, starting Day 15 (_____/____/____) (YYYY/MM/DD) and every Monday and Friday, thereafter. Target CSA level = 200-300 mcg/L. Daily weight (kg) before breakfast. Record intake and output daily Diet:______Monitoring during ATG infusions (See Note #2 on back of this page) Day 1: • Vital signs prior to infusion, then q 15 min x 1 h, q 30 min x 1 h, then q 1 h until infusion is completed • Monitor for allergic reactions continuously during the first 15 minutes and then q 1 h until infusion completed: fever (temperature ≥ 38°C), chills, hives, rash, pruritus, SBP change (increase or decrease of ≥ 20% from pre-infusion reading), shortness of breath, chest pain. • Stop infusion and notify MD if reaction(s) observed Days 2-5: • Vital signs q 30 min x 1 h, then q 2 h until infusion is completed • Monitor for allergic reactions (see Day 1) every four hours • Stop infusion and notify MD if reaction(s) observed

Doctor’s Signature: PRINT NAME: Pager: DISTRIBUTION: White Original - Chart Yellow Copy - Pharmacy Page 1 of 4

PR 10033 (2008/12/07) NOTES:

1. Ensure that patient has central venous catheter (CVC) access. To avoid delay in therapy infuse ATG through a peripheral line only if central venous access is not feasible/available. 2. If patient experienced an allergic reaction or abnormal vital signs (temperature ≥ 38°C, SBP decrease or increase of ≥ 20% from pre-infusion reading) during the previous day’s infusion, consider extending the infusion rate to 12 hours and/or more frequent monitoring (write orders on a Physician’s Order Form). 3. Serum sickness manifesting as fever, arthralgia, lymphadenopathy and cutaneous eruptions (morbilliform rash) occurs in the majority of patients with aplastic anemia treated with ATG. Symptoms generally develop within 7 to 14 days after initiating ATG. Prescribe hydrocortisone sodium succinate (Solu-Cortef®) 100 mg IV q6h. 4. Prednisone taper. Consider graduated taper over 5 days, starting on day 15. Write tapering orders on a Physician’s Order Form.

Rabbit ATG Infusion Dose (3.75 mg/kg/day) Patient Prednisone Cyclosporine Weight Day 1 Dose Dose for (1 mg/kg/day) (2.5 mg/kg) (kg) (2.5 mg Test Days 2-5 Rounded to 5 mg Rounded to 25 mg Dose has been (Rounded to 25 mg) subtracted) (mg) (mg) 45 172.5 175 45 100 46-47 172.5 175 45 125 48-49 172.5 175 50 125 50-52 197.5 200 50 125 53-54 197.5 200 55 125 55-56 197.5 200 55 150 57 222.5 225 55 150 58-62 222.5 225 60 150 63 222.5 225 65 150 64-65 247.5 250 65 150 66-67 247.5 250 65 175 68-70 247.5 250 70 175 71-72 272.5 275 70 175 73-74 272.5 275 75 175 75-76 272.5 275 75 200 77 297.5 300 75 200 78-82 297.5 300 80 200 83 297.5 300 85 200 84-85 322.5 325 85 200 86-87 322.5 325 85 225 88-89 322.5 325 90 225 90-92 347.5 350 90 225 93-94 347.5 350 95 225 95-96 347.5 350 95 250 97 372.5 375 95 250 98-100 372.5 375 100 250

PR 10033 (2008/12/07) PHYSICIAN’S ORDERS

Signature TIME of & nurse DATE

YYYY/MM/DD

RABBIT Antithymocyte Globulin (ATG, Thymoglobulin®) Orders for Aplastic Anemia Yes No Doctor must check off appropriate orders. Have the following medication readily available in the patient’s medication bin: epinephrine 1:1,000 inj methylprednisolone (Solu-Medrol®), 125mg diphenhydramine (Benadryl®) Inj, 50mg salbutamol inhaler + spacer device Monitor for signs or symptoms of serum sickness (see Note #3 on back of this page). Notify MD if signs or symptoms of serum sickness develop. Height:______cm Weight:______kg BSA______m2 Day 1: TEST DOSE _____/_____/_____(YYYY/MM/DD) Pre-medication NOT to be given PRIOR to test dose Rabbit ATG (Thymoglobulin®) 0.5mL (2.5mg) in 100mL of Normal Saline IV to run over 1 hour through 0.2-micron in-line filter Vital Signs prior to test dose infusion, then q 15 min x 1 hour. Monitor for allergic reactions: fever (temperature ≥ 38°C), chills, hives, rash, pruritus, hyper- or hypotension (increased or decreased SBP of ≥ 20% from pre-infusion reading), shortness of breath, chest pain continually during the first 15 minutes, then q15 minutes until infusion completed. If reaction(s) observed stop infusion and notify MD. If no allergic reaction within 1 hour of starting Test Dose proceed with Day 1 infusion Days 1-5: PRE MEDICATION (Begin only if patient tolerates ATG Test Dose) prednisone 1mg/kg/day rounded to nearest 5mg (=_____mg -see back of this page for rounded dose) po, 60 minutes prior to first dose (Day 1) of ATG, then daily x 4 days 60 minutes prior to each subsequent ATG dose (total = 5 doses). acetaminophen 1000 mg po, 60 minutes prior to first dose (Day 1) ofATG, then daily x 4 days 60 minutes prior to each subsequent ATG dose (total = 5 doses). diphenhydramine (Benadryl®) 50 mg IV, 60 minutes prior to first dose (Day 1) of ATG, then daily x 4 days 60 minutes prior to each subsequent ATG dose (total = 5 doses).

Doctor’s Signature: PRINT NAME: Pager: DISTRIBUTION: White Original - Chart Yellow Copy - Pharmacy Page 2 of 4

PR 10033 (2008/12/07) NOTES:

1. Ensure that patient has central venous catheter (CVC) access. To avoid delay in therapy infuse ATG through a peripheral line only if central venous access is not feasible/available. 2. If patient experienced an allergic reaction or abnormal vital signs (temperature ≥ 38°C, SBP decrease or increase of ≥ 20% from pre-infusion reading) during the previous day’s infusion, consider extending the infusion rate to 12 hours and/or more frequent monitoring (write orders on a Physician’s Order Form). 3. Serum sickness manifesting as fever, arthralgia, lymphadenopathy and cutaneous eruptions (morbilliform rash) occurs in the majority of patients with aplastic anemia treated with ATG. Symptoms generally develop within 7 to 14 days after initiating ATG. Prescribe hydrocortisone sodium succinate (Solu-Cortef®) 100 mg IV q6h. 4. Prednisone taper. Consider graduated taper over 5 days, starting on day 15. Write tapering orders on a Physician’s Order Form.

PR 10033 (2008/12/07) PHYSICIAN’S ORDERS

Signature TIME of & nurse DATE

YYYY/MM/DD

RABBIT Antithymocyte Globulin (ATG, Thymoglobulin®) Orders for Aplastic Anemia Yes No Doctor must check off appropriate orders. PRN Medication diphenhydramine (Benadryl®) 50 mg IV q 4h prn for rash acetaminophen 500-1000 mg po q4h prn for temperature ≥ 38ºC (total of scheduled and prn doses must not exceed 4,000 mg daily) Day 1: ATG INFUSION _____/_____/_____(YYYY/MM/DD) Rabbit ATG 3.75mg/kg (=______mg-see back of this page for “Day 1 Infusion Dose”) in 1000 mL of Normal Saline to IV run over 12 hours through a 0.2-micron in-line filter. Day 2: ATG INFUSION _____/_____/_____(YYYY/MM/DD) If no allergic reactions observed with Day 1 infusion, administer rabbit ATG 3.75mg/kg rounded to nearest 25mg (=______mg – see back of this page “Infusion for Days 2-5”) in 1000 mL of Normal Saline IV to run over 6 hours through a 0.2-micron in-line filter. If reaction(s) observed with Day 1 infusion, increase infusion rate to 12 hours (see Note #2 on back of this page). Day 3: ATG INFUSION _____/_____/_____(YYYY/MM/DD) If no allergic reactions observed with Day 2 infusion administer rabbit ATG 3.75mg/kg rounded to nearest 25mg (=______mg -see back of this page “Infusion for Days 2-5”) in 1000 mL of Normal Saline IV to run over 6 hours through a 0.2-micron in-line filter. If reaction(s) observed with Day 2 infusion, increase infusion rate to 12 hours (see Note #2 on back of this page). Day 4: ATG INFUSION _____/_____/_____(YYYY/MM/DD) If no allergic reactions observed with Day 3 infusion administer rabbit ATG 3.75 mg/kg rounded to nearest 25mg (=______mg -see back of this page “Infusion for Days 2-5”) in 1000 mL of Normal Saline IV to run over 6 hours through a 0.2-micron in-line filter. If reaction(s) observed with Day 3 infusion, increase infusion rate to 12 hours (see Note #2 on back of this page).

Doctor’s Signature: PRINT NAME: Pager: DISTRIBUTION: White Original - Chart Yellow Copy - Pharmacy Page 3 of 4

PR 10033 (2008/12/07) NOTES:

1. Ensure that patient has central venous catheter (CVC) access. To avoid delay in therapy infuse ATG through a peripheral line only if central venous access is not feasible/available. 2. If patient experienced an allergic reaction or abnormal vital signs (temperature ≥ 38°C, SBP decrease or increase of ≥ 20% from pre-infusion reading) during the previous day’s infusion, consider extending the infusion rate to 12 hours and/or more frequent monitoring (write orders on a Physician’s Order Form). 3. Serum sickness manifesting as fever, arthralgia, lymphadenopathy and cutaneous eruptions (morbilliform rash) occurs in the majority of patients with aplastic anemia treated with ATG. Symptoms generally develop within 7 to 14 days after initiating ATG. Prescribe hydrocortisone sodium succinate (Solu-Cortef®) 100 mg IV q6h. 4. Prednisone taper. Consider graduated taper over 5 days, starting on day 15. Write tapering orders on a Physician’s Order Form.

PR 10033 (2008/12/07) PHYSICIAN’S ORDERS

Signature TIME of & nurse DATE

YYYY/MM/DD

RABBIT Antithymocyte Globulin (ATG, Thymoglobulin®) Orders for Aplastic Anemia Yes No Doctor must check off appropriate orders. Day 5: ATG INFUSION _____/_____/_____(YYYY/MM/DD) If no allergic reactions observed with Day 4 infusion administer rabbit ATG 3.75mg/kg rounded to nearest 25mg (=______mg -see back of page this page “Infusion for Days 2-5”) in 1000mL of Normal Saline IV to run over 6 hours through a 0.2-micron in-line filter. If reaction(s) observed with Day 4 infusion, increase infusion rate to 12 hours (see Note #2 on back of this page). Day 6: _____/_____/_____(YYYY/MM/DD) prednisone 1 mg/kg rounded to nearest 5mg (= _____ mg-see back of this page for rounded dose) po daily with breakfast x 9 doses. Day 15: _____/_____/_____(YYYY/MM/DD) Contact the physician regarding tapering of prednisone dose (see Note #4 on back this page). cyclosporine 2.5mg/kg rounded to nearest 25mg (= ______mg -see back of this page for rounded dose) po BID for a minimum duration of 6 months

Doctor’s Signature: PRINT NAME: Pager: DISTRIBUTION: White Original - Chart Yellow Copy - Pharmacy Page 4 of 4

PR 10033 (2008/12/07) NOTES:

1. Ensure that patient has central venous catheter (CVC) access. To avoid delay in therapy infuse ATG through a peripheral line only if central venous access is not feasible/available. 2. If patient experienced an allergic reaction or abnormal vital signs (temperature ≥ 38°C, SBP decrease or increase of ≥ 20% from pre-infusion reading) during the previous day’s infusion, consider extending the infusion rate to 12 hours and/or more frequent monitoring (write orders on a Physician’s Order Form). 3. Serum sickness manifesting as fever, arthralgia, lymphadenopathy and cutaneous eruptions (morbilliform rash) occurs in the majority of patients with aplastic anemia treated with ATG. Symptoms generally develop within 7 to 14 days after initiating ATG. Prescribe hydrocortisone sodium succinate (Solu-Cortef®) 100 mg IV q6h. 4. Prednisone taper. Consider graduated taper over 5 days, starting on day 15. Write tapering orders on a Physician’s Order Form.

PR 10033 (2008/12/07) Bortezomib (Velcade®)

Indications Second-line therapy for patients with multiple myeloma

Drug Regimen i. Induction Bortezomib 1.3 mg/m2 IV days 1, 4, 8, 11 Repeat cycle every 21 days for 8 cycles

ii. Maintenance Bortezomib 1.3 mg/m2 IV days 1, 8, 15, 22 Repeat cycle every 35 days for cycle 9-11

Optional Dexamethasone 40 mg p.o. days 1-4, 9-12, 17-20 of cycles 1-4 Repeat cycle every 35 days

40 mg p.o. days 1-4 of cycles 5-9 Repeat every 28 days

Maximum 280 days

Cycle Frequency 3 weeks for cycle 1-8 5 weeks for cycle 9-11

Dose Hematologic toxicity grade III/IV thrombocytopenia and neutropenia consider Modification 50% dose reduction Criteria Non-hematologic toxicity grade III/IV ex neuropathy/GI toxicity 50% dose reduction

Cost Cost $2000 per dose

References Richardson, P.G., et al., Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med, 2005. 352(24): p. 2487-98.

Abbreviations: IV = intravenously; p.o. = by mouth

Page 4 of 61 Appendix B

CBV

Indications High-dose therapy for lymphoma (Transplant Protocol)

Drug Regimen Day - 7 Etoposide 2400 mg/m2 IV by continuous infusion over 24 hours

Day -6 Hyperhydration D5 NS with 20 mEq KCl and 0.5 g MgSO4/L at 125 mL/m2/hour from day -6 to -1

Day - 5 Cyclophosphamide 1800 mg/m2 IV in 500 mL NS over 2 hours

Day -4 Cyclophosphamide 1800 mg/m2 IV in 500 mL NS over 2 hours

Day -3 Cyclophosphamide 1800 mg/m2 IV in 500 mL NS over 2 hours

Day -2 Cyclophosphamide 1800 mg/m2 IV in 500 mL NS over 2 hours

Day -1 Carmustine 500 mg/m2 IV in 500 mL D5W over 4 hours Hyperhydration until 12 PM (see day -6)

Day 0 Stem Cell Infusion

Cycle Frequency Single course only

Cost $1200 for single course

References Wheeler, C., et al., Cyclophosphamide, carmustine, and etoposide with autologous bone marrow transplantation in refractory Hodgkin's disease and non-Hodgkin's lymphoma: a dose-finding study. J Clin Oncol, 1990. 8(4): p. 648-56.

Abbreviations: D5 NS = 5% dextrose with normal saline; D5W = 5 % dextrose IV = intravenously; KCl = potassium chloride; MgSO4 = magnesium sulphate; NS = normal saline

Appendix B Page 5 of 61

Chlorambucil

Indications First-line therapy for indolent lymphoma/CLL

Drug Regimen Chlorambucil 0.1-0.2 mg/kg/day p.o. x 28 days (round dose off to nearest 2 mg) Or 8 mg/m2/day p.o. x 14 days (round dose off to nearest 2 mg)

May also add Prednisone 50 mg p.o. daily for 5-10 days

Cycle Frequency Repeat every 28 days until progression, toxicity or stable symptomatic improvement

Dose Hematologic Toxicity Modification If absolute neutrophil count < 1.0 x 109/L hold dose for 1 week Criteria

Cost $140 per month (patient’s cost)

Abbreviations: CLL = Chronic lymphocytic leukemia; p.o. = by mouth

Page 6 of 61 Appendix B

Chlorambucil + Rituximab

Indications First-line therapy for indolent lymphoma/CLL

Drug Regimen Premedications Acetaminophen 1000 mg p.o. and diphenhydramine 50 mg IV prior to rituximab

Rituximab 375 mg/m2 IV in 500 mL NS on day 1 of each cycle of chlorambucil (Note: begin infusion at 50 mg/hour, if no infusion related reactions are experienced by the patient escalate by 50 mg/hour every 30 minutes to a maximum of 400 mg/hour)

Chlorambucil 0.1-0.2 mg/kg/day p.o. x 28 days (round dose off to nearest 2 mg)

Or 8 mg/m2/day p.o. x 14 days (round dose off to nearest 2 mg)

Prednisone May also add 50 mg p.o. daily for 5-10 days (Note: If given, prednisone should be started day 1, prior to rituximab as part of premedications)

Cycle Frequency Repeat every 28 days (or as specified by chlorambucil protocol) until progression, toxicity, or stable symptomatic improvement

Dose Hematologic Toxicity Modification If absolute neutrophil count < 1.0 x 109/L hold dose for 1 week Criteria

Cost Rituximab $2925 per cycle, chlorambucil $140 per cycle (patient’s cost)

Abbreviations: CLL = Chronic lymphocytic leukemia; IV = intravenously; NS = normal saline; p.o. = by mouth

Appendix B Page 7 of 61

CHOMP

Indications First-line treatment for aggressive histology lymphoma at high risk or confirmed CNS involvement

Therapy of Burkitt's lymphoma

Drug Regimen Part A Cyclophosphamide 1200 mg/m2 by IV in 500 mL NS over 30 minutes day 1 Doxorubicin 40 mg/m2 by IV push day 1 Vincristine 1.4 mg/m2 (maximum 2 mg) by IV in 50 mL NS over 15 minutes - day 1 Prednisone 100 mg p.o. daily for 5 days – days 1-5 Methotrexate 12 mg IT in preservative-free NS (total 5 mL) – day 1

Part B Methotrexate 3000 mg/m2 IV (in 1 L NS) over 4 hours day 10 Methotrexate 12 mg IT in preservative-free NS (total 5 mL) – day 10 Leucovorin 25 mg/m2 IV q6h x 12 doses to begin 24 hours after starting Methotrexate (and continued until MTX level < 0.1 μmol/L)

Cycle Frequency Repeat every 21 days (for a usual total of 6-9 cycles)

Dose Hematologic Toxicity Modification Hold dose for 1 week if absolute neutrophil count < 1.0 x 109/L or platelets < 75 x Criteria 109/L

Filgrastim support should be considered after first episode of febrile neutropenia or dose delay ≥ 1 week

Renal Failure If serum creatinine > 265 μmol/L omit part B

Hepatic Dysfunction If bilirubin = 26-51 μmol/L or AST = 60-180 IU/L, reduce doxorubicin to 75% dose and vincristine to 50% dose

If bilirubin = 52-85 μmol/L or AST > 180 IU/L, reduce cyclophosphamide to 75% dose, doxorubicin to 50% dose and vincristine to 25% dose

If bilirubin > 85 μmol/L, omit doxorubicin and vincristine

Cost $275 per cycle (does not include hospitalization cost)

References Bernstein, J.I., et al., Combined modality therapy for adults with small noncleaved cell lymphoma (Burkitt's and non-Burkitt's types). J Clin Oncol, 1986. 4(6): p. 847-58.

Abbreviations: IT = intrathecally; IV = intravenously; MTX = methotrexate; NS = normal saline; p.o. = by mouth

Page 8 of 61 Appendix B

CHOMP (Inpatient Orders)

Physician’s Orders

Patient Identification

Note: Extracted from the Sunnybrook Health Sciences Centre Inpatient Order Sheet CHOMP - Part B (High Dose Methotrexate) Chemotherapy for High Grade Lymphoma (Inpatient Portion) YES NO Doctor must check off Yes/No for all orders Patient received Part A (CHOMP) of regimen Prechemotherapy blood work (if not done prior to admission): CBC, differential, electrolytes, blood glucose, calcium profile, liver profile, renal profile, LDH, uric acid Serum methotrexate levels daily starting the day following methotrexate administration, and continuing until methotrexate level is < 0.1цmol/L Other daily blood work: Renal profile, calcium profile, electrolytes Urine pH b.i.d. Hold chemotherapy until Doctor approves blood work results, and urine pH ≥7.0 Allopurinol 300 mg p.o. daily (starting on day 1) for cycle 1 only Sodium bicarbonate 600 mg p.o. t.i.d. (starting on day 1) Hydration: IV D5W with 150 mmol/L sodium bicarbonate to run @ (80 mL/m2/hr)______mL/hr starting the morning of IV methotrexate and to continue until methotrexate level is < 0.1цmol/L Monitor intake and output daily ANTIEMETIC THERAPY Ondansetron 8 mg p.o. q12h x 2 doses, on day 1 starting 30 minutes prior to IV methotrexate Dexamethasone 12 mg p.o. x 1 dose, 30 minutes prior to IV methotrexate, on day 1 Dexamethasone 4 mg p.o. b.i.d. x 6 doses starting day 2 Prochlorperazine 10 mg p.o./IV q4h p.r.n. for nausea and vomiting CHEMOTHERAPY ADMINISTRATION Date chemotherapy is to be given:_____/_____/_____(YY/MM/DD) Height:______cm Weight:______kg BSA:______m2 Methotrexate (3000 mg/m2)______mg IV in 1 L normal saline to run over 4 hours Folinic Acid (25 mg/m2)______mg IV q6h to begin 24 hours after starting the methotrexate infusion; continue until methotrexate level is < 0.1цmol/L Discontinue folinic acid & hydration only when methotrexate level is < 0.1цmol/L INTRATHECAL CHEMOTHERAPY Date intrathecal chemotherapy is to be given:____/____/___(YY/MM/DD) Preservative-free methotrexate 12 mg in normal saline (total volume of 5 mL) for intrathecal injection (to be given by doctor) Doctor’s Signature: Date (YY/MM/DD):

Appendix B Page 9 of 61

CHOP

Indications First-line therapy for aggressive histology lymphoma Salvage therapy for indolent lymphoma, CLL

Drug Regimen Cyclophosphamide 750 mg/m2 by IV in 50 or 500 mL NS over 30 minutes day 1

Doxorubicin 50 mg/m2 by IV push day 1

Vincristine 1.4 mg/m2 (maximum 2 mg) by IV in 50 mL NS over 15 minutes day 1

Prednisone 100 mg p.o. daily days 1-5

Cycle Frequency Repeat every 21 days (for a usual total of 6-8 cycles)

Dose Hematologic Toxicity Modification Hold dose for 1 week if absolute neutrophil count < 1.0 x 109/L or platelets < 75 x Criteria 109/L

Filgrastim support should be considered after first episode of febrile neutropenia or dose delay ≥ 1 week

Hepatic Dysfunction If bilirubin = 26-51 μmol/L or AST = 60-180 IU/L, reduce doxorubicin to 75% dose and vincristine to 50% dose

If bilirubin = 52-85 μmol/L or AST > 180 IU/L, reduce cyclophosphamide to 75% dose, doxorubicin to 50% dose and vinblastine to 25% dose

If bilirubin > 85 μmol/L, omit doxorubicin and vincristine

Cost $60 per cycle

References Gordon, L.I., et al., Comparison of a second-generation combination chemotherapeutic regimen (m-BACOD) with a standard regimen (CHOP) for advanced diffuse non-Hodgkin's lymphoma. N Engl J Med, 1992. 327(19): p. 1342-9.

Abbreviations: CLL = Chronic lymphocytic leukemia; IV = intravenously; NS = normal saline; p.o. = by mouth

Page 10 of 61 Appendix B

CHOP + Rituximab

Indications First-line therapy for diffuse large B-cell lymphoma

Drug Regimen Premedications Acetaminophen 1000 mg p.o. and diphenhydramine 50 mg IV prior to rituximab

Rituximab 375 mg/m2 IV in 500 mL NS on day 1 of each cycle of CHOP (Note: begin infusion at 50 mg/hour, if no infusion related reactions are experienced by the patient escalate by 50 mg/hour every 30 minutes to a maximum of 400 mg/hour)

Cyclophosphamide 750 mg/m2 by IV in 50 or 500 mL NS over 30 minutes day 1

Doxorubicin 50 mg/m2 by IV push day 1

Vincristine 1.4 mg/m2 (maximum 2 mg) by IV in 50 mL NS over 15 minutes day 1

Prednisone 100 mg p.o. daily days 1 to 5 (Note: Prednisone should be started day 1, prior to rituximab as part of premedications)

Cycle Frequency Repeat every 21 days (for a usual total of 6-8 cycles)

Dose Hematologic Toxicity Modification Hold dose for 1 week if absolute neutrophil count < 1.0 x 109/L or platelets < 75 x Criteria 109/L

Filgrastim support should be considered after first episode of febrile neutropenia or dose delay ≥ 1 week

Hepatic Dysfunction If bilirubin = 26-51 μmol/L or AST = 60-180 IU/L, reduce doxorubicin to 75% dose and vincristine to 50% dose

If bilirubin = 52-85 μmol/L or AST > 180 IU/L, reduce cyclophosphamide to 75% dose, doxorubicin to 50% dose and vinblastine to 25% dose

If bilirubin > 85 μmol/L, omit doxorubicin and vincristine

Cost $2985 per cycle

References Coiffier, B., et al., CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med, 2002. 346(4): p. 235-42.

Hiddemann, W., et al., Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood, 2005. 106(12): p. 3725-32.

Abbreviations: IV = intravenously; NS = normal saline; p.o. = by mouth

Appendix B Page 11 of 61

Cladribine (2-CDA)

Indications First-line therapy for hairy cell lymphoma

Drug Regimen Cladribine 0.1 mg/kg/day CIV x 7 days

Or 0.12-0.14 mg/kg/day IV in 500 mL NS over 2 hours daily x 5 days

Cycle Frequency Single course only

Dose Caution with renal insufficiency since 2-CDA is 10-30% excreted in urine Modification Criteria

Cost $2500 for single course

References Piro, L.D., et al., Lasting remissions in hairy-cell leukemia induced by a single infusion of 2-chlorodeoxyadenosine. N Engl J Med, 1990. 322(16): p. 1117-21.

Morton, J., et al., High response rates with short infusional 2- chlorodeoxyadenosine in de novo and relapsed low-grade lymphoma. Australian and New Zealand Lymphoma Study Group. Br J Haematol, 1996. 95(1): p. 110-5.

Abbreviations: CIV = continuous intravenous infusion; IV = intravenously; NS = normal saline

Page 12 of 61 Appendix B

CVP (IV)

Indications First-line/salvage therapy for indolent lymphoma/CLL

Drug Regimen Cyclophosphamide 800 mg/m2 IV in 50mL or 500mL NS over 30 minutes day 1

Vincristine 1.4 mg/m2 (maximum 2 mg) IV in 50 mL NS over 15 minutes day 1

Prednisone 100 mg/day p.o. days 1 to 5

Cycle Frequency Repeat every 21 days (usually for a total of 6 to 8 cycles)

Dose Hematologic Toxicity Modification If absolute neutrophil count < 1.0 x 109/L hold dose for 1 week Criteria Hepatic Dysfunction If bilirubin = 25 – 50 μmol/L or AST = 60 – 180 IU/L, reduce vincristine to 50% dose

If bilirubin = 51 – 85 μmol/L or AST > 180 IU/L, reduce vincristine to 25% dose and cyclophosphamide to 75% dose

If bilirubin > 85 μmol/L, omit cyclophosphamide and vincristine

Cost $20 per cycle

References Marcus, R., et al., CVP chemotherapy plus rituximab compared with CVP as first- line treatment for advanced follicular lymphoma. Blood, 2005. 105(4): p. 1417- 23.

Abbreviations: CLL = Chronic lymphocytic leukemia; IV = intravenously; NS = normal saline; p.o. = by mouth

Appendix B Page 13 of 61

CVP (IV) + Rituximab

Indications First-line/salvage therapy for indolent lymphoma/CLL

Drug Regimen Premedications Acetaminophen 1000 mg p.o. and diphenhydramine 50 mg IV prior to rituximab

Rituximab 375 mg/m2 IV in 500 mL NS on day 1 of each cycle of CVP (Note: begin infusion at 50 mg/hour, if no infusion related reactions are experienced by the patient escalate by 50 mg/hour every 30 minutes to a maximum of 400 mg/hour)

Cyclophosphamide 800 mg/m2 IV in 50 mL or 500 mL NS over 30 minutes day 1

Vincristine 1.4 mg/m2 IV (maximum 2 mg) in 50 mL NS over 15 minutes day 1

Prednisone 100 mg/day p.o. days 1 to 5 (Note: Prednisone should be started day 1, prior to rituximab as part of premedications)

Cycle Frequency Repeat every 21 days (usually for a total of 6 to 8 cycles)

If bilirubin = 51 – 85 μmol/L or AST > 180 IU/L, reduce vincristine to 25% dose and cyclophosphamide to 75% dose

If bilirubin > 85 μmol/L, omit cyclophosphamide and vincristine

Cost $2945 per cycle

References Marcus, R., et al., CVP chemotherapy plus rituximab compared with CVP as first- line treatment for advanced follicular lymphoma. Blood, 2005. 105(4): p. 1417- 23.

Abbreviations: CLL = Chronic lymphocytic leukemia; IV = intravenously; NS = normal saline; p.o. = by mouth

Page 14 of 61 Appendix B

CVP (Oral)

Indications First-line/salvage therapy for indolent lymphoma/CLL

Drug Regimen Cyclophosphamide 400 mg/m2/day p.o. days 1-5 (round off to closest 25 mg)

Vincristine 1.4 mg/m2 (maximum 2 mg) IV in 50 mL NS over 15 minutes day 1

Prednisone 100 mg/day p.o. days 1-5 (round off to closest 50 mg)

Cycle Frequency Repeat every 21 days (usually for a total of 6 to 8 cycles)

If bilirubin = 51 – 85 μmol/L or AST > 180 IU/L, reduce vincristine to 25% dose and cyclophosphamide to 75% dose

If bilirubin > 85 μmol/L, omit cyclophosphamide and vincristine

Cost $30 per cycle

References Bagley, C.M., Jr., et al., Advanced lymphosarcoma: intensive cyclical combination chemotherapy with cyclophosphamide, vincristine, and prednisone. Ann Intern Med, 1972. 76(2): p. 227-34.

Abbreviations: CLL = chronic lymphocytic leukemia; IV = intravenously; NS = normal saline; p.o. = by mouth

Appendix B Page 15 of 61

CVP (Oral) + Rituximab

Indications First-line/salvage therapy for indolent lymphoma/CLL

Drug Regimen Premedications Acetaminophen 1000 mg p.o. and diphenhydramine 50 mg IV prior to rituximab

Cyclophosphamide 400 mg/m2/day p.o. days 1-5 (round off to closest 25 mg)

Vincristine 1.4 mg/m2 (maximum 2 mg) IV in 50 mL NS over 15 minutes day 1

Prednisone 100 mg/day p.o. days 1-5 (round off to closest 50 mg)

Cycle Frequency Repeat every 21 days (usually for a total of 6 to 8 cycles)

If bilirubin = 51 – 85 μmol/L or AST > 180 IU/L, reduce vincristine to 25% dose and cyclophosphamide to 75% dose

If bilirubin > 85 μmol/L, omit cyclophosphamide and vincristine

Cost $2955 per cycle

Abbreviations: CLL = chronic lymphocytic leukemia; IV = intravenously; NS = normal saline; p.o. = by mouth

Page 16 of 61 Appendix B

DHAP

Indications Salvage therapy for aggressive histology lymphoma

Drug Regimen Cisplatin 100 mg/m2 CIV over 24 hours day 1

Cytarabine 2000 mg/m2 IV in 250 mL NS over 3 hours repeat 12 hours later day 2

Dexamethasone 40 mg p.o. or IV daily days 1-4

Cycle Frequency Repeat every 21-28 days

Dose Hematologic Toxicity Modification If absolute neutrophil count < 1.0 x 109/L hold dose for 1 week Criteria Renal Failure If creatinine clearance = 0.5 – 1.0 mL/second or serum creatinine = 136-185 μmol/L reduce cisplatin to 50% dose

If creatinine clearance < 0.5 mL/second or serum creatinine > 185 μmol/L omit cisplatin

Cost $295 per cycle (does not include hospitalization costs)

References Velasquez, W.S., et al., Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood, 1988. 71(1): p. 117-22.

Abbreviations: CIV = continuous intravenous infusion; IV = intravenously; NS = normal saline; p.o. = by mouth

Appendix B Page 17 of 61

DHAP (Inpatient Orders)

Physician’s Orders

Patient Identification

Note: Extracted from the Sunnybrook Health Sciences Centre Inpatient Order Sheet DHAP Chemotherapy for Lymphoma YES NO Doctor must check off Yes/No for all orders Prechemotherapy blood work (if not done prior to admission): CBC, differential, electrolytes, blood glucose, calcium profile, liver profile, renal profile, LDH, uric acid Hold chemotherapy until blood work satisfactory, urine pH > 7, third space fluid (if present) is drained Allopurinol 300 mg p.o. daily HYDRATION IV normal saline with 4 mmol/L magnesium sulphate + 20 mmol/L KCl + 20 g/L mannitol at: 250 mL/hour x 6 hours pre-cisplatin 125 mL/hour during cisplatin 200 mL/hour x 6 hours following completion of cisplatin Then change to IV normal saline at 75 mL/hour ANTIEMETIC THERAPY Ondansetron 8 mg p.o. 30 minutes prior to chemotherapy on day 1, then q12h x 3 doses Prochlorperazine 10 mg p.o./IV q4h prn (for nausea) CHEMOTHERAPY ADMINISTRATION Height:______cm Weight:______kg BSA:______m2 DAY 1 (YY/MM/DD): | | | Dexamethasone 40 mg p.o. or IV in 50 mL normal saline over 15 minutes (with breakfast) Cisplatin (33 mg/m2) ______mg in 1 L normal saline + 20 g/L mannitol to run at 125 mL/hour x 3 bags (i.e. 100 mg/m2 over 24 hours) DAY 2 (YY/MM/DD): | | | 2 To begin immediately following completion of cisplatin: cytarabine (2000 mg/m ) ______mg in 250 mL normal saline over 3 hours q12h x 2 doses Dexamethasone 40 mg p.o. or IV in 50 mL normal saline over 15 minutes (with breakfast) DAY 3 (YY/MM/DD): | | | Dexamethasone 40 mg p.o. or IV in 50 mL normal saline over 15 minutes (with breakfast) DAY 4 (YY/MM/DD): | | | Dexamethasone 40 mg p.o. or IV in 50 mL normal saline over 15 minutes (with breakfast) Doctor’s Signature: Date (YY/MM/DD):

Page 18 of 61 Appendix B

DPACE

Indications Salvage therapy for multiple myeloma

Drug Regimen Dexamethasone 40 mg p.o./day days 1-4 Cisplatin 10 mg/m2 IV daily by continuous infusion days 1-4 Adriamycin 10 mg/m2 IV daily by continuous infusion days 1-4 Cyclophosphamide 400 mg/m2 IV daily by continuous infusion days 1-4 Etoposide 40 mg/m2 IV daily by continuous infusion days 1-4

Cycle Frequency Repeat every 4-6 weeks

Dose Hematologic Toxicity Modification Hold dose for 1 week if absolute neutrophil count < 1.0 x 109/L or platelets < 75 x Criteria 109/L

Consider filgrastim support

Renal Failure If creatinine > 265 μmol/L omit cisplatin

Cost $210 per cycle

References Barlogie B, Desikan R, Munshi N, et al. Single course D.T. pace anti- angiochemotherapy effects CR in plasma cell leukemia and fulminant multiple myeloma (MM). Blood. Nov 1998, Vol 92, No 10, Suppl 1, Part 2: 273b (Abstract #4180).

Munshi N, Desikan R, Zangari M, et al. Chemoangiotherapy with DT-Pace for previously treated multiple myeloma (MM). Blood. Nov. 1999, Vol 94, No 10, Suppl 1, Part 1: 123a (Abstract#540)

Abbreviations: IV = intravenously; p.o. = by mouth

Appendix B Page 19 of 61

ESHAP

*Indications Salvage therapy for aggressive histology lymphoma

Drug Regimen Etoposide 40-60 mg/m2/day in 250 mL of NS over 30 minutes days 1-4

Methylprednisolone 500 mg IV in 100 mL NS over 15 minutes days 1-5

Cisplatin 25 mg/m2/day CIV in 500 mL NS over 24 hour days 1-4

Cytarabine 2000 mg/m2 IV in 250 mL NS over 2 hours day 5

Cycle Frequency Repeat every 21 – 28 days

Dose Hematologic Toxicity Modification If absolute neutrophil count < 1.0 x 109/L or platelets < 75 x 109/L, hold for 1 Criteria week

Hepatic Dysfunction If bilirubin = 26-51 μmol/L or AST = 60-180 IU/L, reduce etoposide to 50% dose If bilirubin = 52-85 μmol/L, reduce etoposide to 25% dose If bilirubin > 85 μmol/L or AST > 180 IU/L, omit etoposide dose

Renal Failure If creatinine clearance = 0.5-1.0 mL/second or serum creatinine = 136-185 μmol/L reduce cisplatin to 50% dose

If creatinine clearance = 0.2-0.8 mL/second or serum creatinine > 130 μmol/L, reduce etoposide to 75% dose

If creatinine clearance < 0.5 mL/second or serum creatinine > 185 μmol/L, omit cisplatin dose

If creatinine clearance < 0.2 mL/second, reduce etoposide to 50%

Cost $300 per cycle

References Cabanillas, F., Non-Hodgkin's lymphomas: a review of the M.D. Anderson experience. Semin Oncol, 1992. 19(1 Suppl 1): p. 11-3.

Velasquez, W.S., et al., ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol, 1994. 12(6): p. 1169-76.

Abbreviations: CIV = continuous intravenous infusion; IV = intravenously; NS = normal saline; p.o. = by mouth

Page 20 of 61 Appendix B

ESHAP (Inpatient Orders)

Physician’s Orders

Patient Identification

Note: Extracted from the Sunnybrook Health Sciences Centre Inpatient Order Sheet ESHAP Protocol - Chemotherapy for Lymphoma YES NO Doctor must check off Yes/No for all orders Prechemotherapy blood work (if not done prior to admission): CBC, differential, electrolytes, blood glucose, calcium profile, liver profile, renal profile, LDH, uric acid Hold chemotherapy until a Doctor approves blood work results Repeat CBC on Day 4 Oral intake of fluids (2 L/day) during cisplatin infusion and for 2 days post cisplatin infusion ANTIEMETIC THERAPY Ondansetron 8 mg p.o. 30 minutes prior to chemotherapy, starting on day 1, then q12h x 9 doses Dexamethasone 8 mg p.o. od x 3 doses, with breakfast, starting on day 6 __/__/__ (YY/MM/DD) Prochlorperazine 10 mg p.o./IV q4h prn for nausea and vomiting CHEMOTHERAPY ADMINISTRATION Height:______cm Weight:______kg BSA:______m2 DAY 1 (YY/MM/DD): | | | Methylprednisolone 500 mg IV in 100 mL normal saline over 15 minutes, give 60 minutes prior to start of chemotherapy Cisplatin (25 mg/m2)______mg IV in 500mL normal saline as continuous infusion over 24 hours Etoposide (40 mg/m2)______mg IV in 250 mL normal saline over 30 minutes with in-line filter (Y- site with cisplatin) DAY 2 (YY/MM/DD): | | | Methylprednisolone 500 mg IV in 100 mL normal saline over 15 minutes, interrupt cisplatin infusion and flush line with 50 mL normal saline before and after methylprednisolone Cisplatin (25 mg/m2)______mg IV in 500 mL normal saline as continuous infusion over 24 hours Etoposide (40 mg/m2)______mg IV in 250 mL normal saline over 30 minute with in-line filter (Y- site with cisplatin) DAY 3 (YY/MM/DD): | | | Methylprednisolone 500 mg IV in 100 mL normal saline over 15 minutes; interrupt cisplatin infusion and flush line with 50 mL normal saline before and after methylprednisolone Cisplatin (25 mg/m2)______mg IV in 500 mL normal saline as continuous infusion over 24 hours Etoposide (40 mg/m2)______mg IV in 250 mL normal saline over 30 minutes with in-line filter (Y- site with cisplatin) DAY 4 (YY/MM/DD): | | | Methylprednisolone 500 mg IV in 100 mL normal saline over 15 minutes; interrupt cisplatin infusion and flush line with 50 mL normal saline before and after methylprednisolone Cisplatin (25 mg/m2)______mg IV in 500 mL normal saline as continuous infusion over 24 hours Etoposide (40 mg/m2)______mg IV in 250 mL normal saline over 30 minutes with in-line filter (Y- site with cisplatin) DAY 5 (YY/MM/DD): | | | Methylprednisolone 500 mg IV in 100 mL normal saline over 15 minutes After completion of cisplatin infusion: Cytarabine (2000 mg/m2)______mg IV in 250 mL normal saline over 2 hours Doctor’s Signature: Date (YY/MM/DD):

Appendix B Page 21 of 61

FCM

Indications First-line or relapsed therapy for indolent lymphoma/mantle cell lymphoma

Drug Regimen Fludarabine 25 mg/m2/day IV in 50-100 mL NS over 15-30 minutes days 1, 2, 3

Cyclophosphamide 200 mg/m2/day IV in 50 mL NS over 30 minutes days 1, 2, 3

Mitoxantrone 8 mg/m2 IV over 30 minutes day 1

Cycle Frequency Repeat every 28 days for a total of 4 cycles

Dose Hematologic Toxicity Modification Hold dose for 1 week if absolute neutrophil count < 1.0 x 109/L or platelets < 75 x Criteria 109/L

Filgrastim support should be considered after first episode of febrile neutropenia or dose delay ≥ 1 week

Hepatic Dysfunction If bilirubin = 26-51 μmol/L or AST = 60-180 IU/L, reduce mitoxantrone to 75% dose

If bilirubin= 52-85 μmol/L or AST > 180 IU/L, reduce cyclophosphamide to 75% dose, mitoxantrone to 50% dose

If bilirubin > 85 μmol/L, omit mitoxantrone

Cost $840 per cycle

References Forstpointner, R., et al., The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood, 2004. 104(10): p. 3064-71.

Abbreviations: IV = intravenously; NS = normal saline

Page 22 of 61 Appendix B

FCM + Rituximab

Indications First-line or relapsed therapy for indolent lymphoma/mantle cell lymphoma

Drug Regimen Premedications Acetaminophen 1000 mg p.o. and diphenhydramine 50 mg IV prior to rituximab

Rituximab 375 mg/m2 IV in 500 mL NS on day 1 of each cycle of FCM (Note: begin infusion at 50 mg/hour, if no infusion related reactions are experienced by the patient escalate by 50 mg/hour every 30 minutes to a maximum of 400 mg/hour)

Fludarabine 25 mg/m2/day IV in 50-100 mL NS over 15-30 minutes days 1, 2 and 3

Cyclophosphamide 200 mg/m2/day IV in 50 mL NS over 30 minutes days 1, 2 and 3

Mitoxantrone 8 mg/m2 IV over 30 minutes day 1

Cycle Frequency Repeat every 28 days for a total of 4 cycles

Dose Hematologic Toxicity Modification Hold dose for 1 week if absolute neutrophil count < 1.0 x 109/L or platelets < 75 x Criteria 109/L

Filgrastim support should be considered after first episode of febrile neutropenia or dose delay ≥ 1 week

Hepatic Dysfunction If bilirubin = 26-51 μmol/L or AST = 60-180 IU/L, reduce mitoxantrone to 75% dose

If bilirubin= 52-85 μmol/L or AST > 180 IU/L, reduce cyclophosphamide to 75% dose, mitoxantrone to 50% dose

If bilirubin > 85 μmol/L, omit mitoxantrone

Cost $840 per cycle

Abbreviations: IV = intravenously; NS = normal saline; p.o. = by mouth

Appendix B Page 23 of 61

Fludarabine

Indications First-line or salvage therapy for indolent lymphoma/CLL

Drug Regimen Fludarabine 25 mg/m2/day IV in 50-100 mL NS over 15- 30 minutes days 1-5 Or 40 mg/m2/day p.o. days 1-5 (round off to nearest 10 mg)

Cycle Frequency Repeat every 28 days until desired response, progression or toxicity

Dose Hematologic Toxicity Modification If absolute neutrophil count < 1.0 x 109/L or platelets < 75 x 109/L, hold for 1 week Criteria Cost $1125 per cycle for oral regimen; $1300 per cycle for intravenous regimen

References Ross, S.R., D. McTavish, and D. Faulds, Fludarabine. A review of its pharmacological properties and therapeutic potential in malignancy. Drugs, 1993. 45(5): p. 737-59.

Redman, J.R., et al., Phase II trial of fludarabine phosphate in lymphoma: an effective new agent in low-grade lymphoma. J Clin Oncol, 1992. 10(5): p. 790-4.

Abbreviations: CLL = chronic lymphocytic leukemia; IV = intravenously; NS = normal saline; p.o. = by mouth

Page 24 of 61 Appendix B

Fludarabine + Rituximab

Indications First-line or salvage therapy for indolent lymphoma/CLL

Drug Regimen Premedications Acetaminophen 1000 mg p.o. and diphenhydramine 50 mg IV prior to rituximab

Rituximab 375 mg/m2 IV in 500 mL NS on day 1 of each cycle of fludarabine (Note: begin infusion at 50 mg/hour, if no infusion related reactions are experienced by the patient escalate by 50 mg/hour every 30 minutes to a maximum of 400 mg/hour)

Fludarabine 25 mg/m2/day IV in 50-100 mL NS over 15-30 minutes days 1-5 or 40 mg/m2/day p.o. days 1-5 (round off to nearest 10 mg)

Cycle Frequency Repeat every 28 days until desired response, progression or toxicity

Dose Hematologic Toxicity Modification If absolute neutrophil count < 1.0 x 109/L or platelets < 75 x 109/L, hold for 1 week Criteria Cost $4050 per cycle for intravenous regimen; $3875 per cycle for oral regimen

References Byrd, J.C., et al., Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic, untreated patients with B-cell chronic lymphocytic leukemia: results from Cancer and Leukemia Group B 9712 (CALGB 9712). Blood, 2003. 101(1): p. 6-14.

Abbreviations: CLL = chronic lymphocytic leukemia; IV = intravenously; NS = normal saline; p.o. = by mouth

Appendix B Page 25 of 61

GDP

Indications Salvage therapy for relapsed Hodgkin’s or non-Hodgkin’s lymphoma

Drug Regimen 0.9% Sodium Chloride 1000 mL IV over 1 hour prechemotherapy day 1

Gemcitabine 1000 mg/m2 IV in 100 mL NS over 30 minutes days 1 and 8

20% Mannitol 250 mL IV over 2 hours (run concurrently with cisplatin) day 1

Cisplatin 40 mg p.o. daily days 1-4

0.9% Sodium Chloride 1000 mL IV over 1 hour post chemotherapy day 1

Cycle Frequency Repeat every 21 days for up to 6 courses

Dose Hematologic Toxicity Modification (Day 1 only) If absolute neutrophil count < 1.0 x 109/L or platelets < 50 x 109/L, Criteria delay 1 week

Renal Dysfunction

CrCl (mL/min) Cisplatin dose > 60 75 mg/m2 on day 1 45-59 37.5 mg/m2 on days 1 and 8 < 45 Delay

Cost $950 per course

References Crump, M., et al., Gemcitabine, dexamethasone, and cisplatin in patients with recurrent or refractory aggressive histology B-cell non-Hodgkin lymphoma: a Phase II study by the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). Cancer, 2004. 101(8): p. 1835-42.

BCCA Protocol Summary for Treatment of Lymphoma with Gemcitabine, Dexamethasone and Cisplatin (GDP). www.bccancer.bc.ca/HPI/ChemotherapyProtocols/Lymphoma/LYGDP.htm.

Abbreviations: CrCl = creatinine clearance; IV = intravenously; NS = normal saline; p.o. = by mouth

Page 26 of 61 Appendix B

HDMVP

Indications First-line therapy for primary CNS lymphoma

Drug Regimen Methotrexate 3500 mg/m2 IV in 1 L NS over 4 hours day 1

Vincristine 1.4 mg/m2 (maximum 2 mg) IV in 50 mL NS over 15 minutes day 1

Procarbazine 100 mg/m2 (round off to the nearest 50 mg) p.o. daily days 1-7 inclusive

Methotrexate 12 mg IT day 1 and day 3

Folinic Acid 25 mg/m2 IV q6h to begin 24 hours after the start of the methotrexate infusion and to be continued until MTX level < 0.1 µmol/L

Cycle Frequency 2-4 cycles given at 4-week intervals

Dose Hematologic Toxicity Modification Hold dose for 1 week if absolute neutrophil count < 1.0 x 109/L or platelets < 75 x Criteria 109/L

Renal Failure Do not give if serum creatinine > 265 µmol/L

Cost $370 per cycle

References Mangel J, Buckstein R, Berinstein NL, Spaner D, Davey P, Perry J and Imrie K. Upfront HDMVP chemotherapy without radiation for the treatment of newly diagnosed primary CNS lymphoma. Blood. Nov. 16, 2001, Vol 98, No 11, page 130a (Abstract #546).

Abbreviations: IT = intrathecally; IV = intravenously; MTX = methotrexate; NS = normal saline; p.o. = by mouth

Appendix B Page 27 of 61

HDMVP (Inpatient Orders)

Physician’s Orders

Patient Identification

Note: Extracted from the Sunnybrook Health Sciences Centre Inpatient Order Sheet HDMVP Chemotherapy for Primary CNS Lymphoma YES NO Doctor must check off Yes/No for all orders Prechemotherapy blood work (if not done prior to admission): CBC, differential, electrolytes, blood glucose, calcium profile, liver profile, renal profile, LDH, uric acid Urine pH BID Hold chemotherapy until blood work satisfactory, urine pH > 7.0, third space fluid (if present) is drained Sodium bicarbonate 600 mg p.o. t.i.d. (starting the day before IV methotrexate) Hydration: IV D5W with 150 mmol/L sodium bicarbonate to run @ (80 mL/m2/hr) ______mL/hr to start the day before IV methotrexate and to continue until methotrexate level is < 0.1 μmol Serum methotrexate levels daily until methotrexate level is < 0.1 μmol Other daily blood work: Renal profile, calcium profile, electrolytes Monitor input and output daily ANTIEMETIC THERAPY Dexamethasone 10 mg IV 30 minutes prior to chemotherapy on day 1 Dexamethasone 8 mg p.o. on day 2 (with breakfast) Ondansetron 8 mg p.o. 30 minutes prior to chemotherapy on day 1, then q12h x 1 dose Prochlorperazine 10 mg p.o./IV 30 minutes prior to chemotherapy on days 2-7 Prochlorperazine 10 mg p.o./IV q4h prn for nausea CHEMOTHERAPY ADMINISTRATION Height:______cm Weight:______kg BSA:______m2 DAY 1 (YY/MM/DD): | | | Methotrexate (3500 mg/m2) ______mg IV in 1 L normal saline to run over 4 hours Vincristine (1.4 mg/m2) ______mg IV push (maximum 2 mg) Procarbazine (100 mg/m2; round off to nearest 50 mg) ______mg p.o. daily to be given on days 1-7 inclusive ___/___/___ - __/___/____ (YY/MM/DD) Methotrexate 12 mg in preservative-free normal saline (total volume of 5 mL) for intrathecal injection on days 1, 3, 5, 8, 10, 12 (to be given by doctor) DAY 2 (YY/MM/DD): | | | Folinic Acid (25 mg/m2) ______mg IV q6h to begin 24 hours after starting the methotrexate infusion: continue until methotrexate level is < 0.1 μmol Doctor’s Signature: Date (YY/MM/DD):

Page 28 of 61 Appendix B

HIDAC Consolidation

Indications Consolidation for AML (under age 60)

Drug Regimen Daunorubicin 45 mg/m2 IV push days 1 and 2 Cytarabine 3000 mg/m2 IV in 250 mL NS over 3 hour q12h days 1, 3 and 5

Cycle Frequency 2-3 cycles 4-6 weeks apart

Dose Hematologic Toxicity Modification If absolute neutrophil count < 1.0 x 109/L or platelets < 50 x 109/L, delay HIDAC Criteria consolidation cycle

Hepatic Failure If bilirubin = 26-51 µmol/L or AST = 60-180 IU/L, reduce daunorubicin to 75% of initial dose

If bilirubin = 52-85 µmol/L or AST > 180 IU/L, reduce daunorubicin to 50% of initial dose

If bilirubin > 85, omit daunorubicin

Cost $1300 per cycle

Abbreviations: AML = acute myelogenous leukemia, IV = intravenously; NS = normal saline

Appendix B Page 29 of 61

HIDAC (Inpatient Orders)

Physician’s Orders

Patient Identification

Note: Extracted from the Sunnybrook Health Sciences Centre Inpatient Order Sheet HIDAC Consolidation - Chemotherapy for Acute Myelogenous Leukemia YES NO Doctor must check off Yes/No for all orders Prechemotherapy blood work (if not done prior to admission): CBC, differential, electrolytes, blood glucose, calcium profile, liver profile, renal profile, LDH, uric acid Hold chemotherapy until a Doctor approves blood work results Prednisolone 1% ophthalmic solution 1 drop both eyes qid x7 days, starting on day 1 Monitor intake and output daily ANTIEMETIC THERAPY Dexamethasone 12 mg p.o. 30 minutes prior to chemotherapy on days 1, 2, 3 and 5 Ondansetron 8mg p.o. 30 minutes prior to chemotherapy and qhs on days 1, 2, 3 and 5 Dexamethasone 8 mg p.o. od x 3 doses, with breakfast starting on day 6 __/__/__(YY/MM/DD) Prochlorperazine 10mg p.o./IV q4h prn for nausea and vomiting CHEMOTHERAPY ADMINISTRATION Height:______cm Weight:______kg BSA:______m2 DAY 1 (YY/MM/DD): | | | Daunorubicin (45 mg/m2)______mg IV push Cytarabine (3000 mg/m2)______mg IV in 250 mL of normal saline to run over 3 hours q12h x 2 doses DAY 2 (YY/MM/DD): | | | Daunorubicin (45 mg/m2)______mg IV push DAY 3 (YY/MM/DD): | | | Cytarabine (3000 mg/m2)______mg IV in 250 mL of normal saline to run over 3 hours q12h x 2 doses DAY 5 (YY/MM/DD): | | | Cytarabine (3000 mg/m2)______mg IV in 250 mL of normal saline to run over 3 hours q12h x 2 doses Doctor’s Signature: Date (YY/MM/DD):

Page 30 of 61 Appendix B

Hyper-CVAD Indications First-line therapy for ALL and lymphoblastic leukemia Drug Regimen Course A Cyclophosphamide 300 mg/m2 IV in 100 mL NS over 3 hours q12h x 6 doses on days 1, 2 and 3 Doxorubicin 50 mg/m2 IV push on day 4 (12 hours after last dose of Cyclophosphamide) Vincristine 2 mg IV in 50 mL NS over 15 minutes on days 4 and 11 Dexamethasone 40 mg IV or p.o. daily days 1-4 and days 11-14 Course B Methotrexate 1000 mg/m2 in 1 L NS over 24 hours day 1 With methotrexate give IV D5W + 150 mEq NaHCO3 at 80 mL/m2/h starting the morning of MTX infusion; continue until MTX level <0.1µmol/L Folinic Acid 25 mg/m2 IV q6h to begin 24 hours after starting MTX infusion; continue until MTX level <0.1µmol/L Sodium Bicarbonate 600 mg PO TID starting on Day 1 (continue until MTX level <0.1µmol/L) Cytarabine 3000 mg/m2 over 2 hours q12h x 4 doses on days 2 and 3 With MTX/high dose cytarabine courses (number 4, 6, and 8) serious toxicities frequently require dose reductions of 25% to 33%: for MTX to 750mg/m2, then 500mg/m2, and to 250mg/m2, for cytarabine to 2g/m2, then 1.5g/m2, and 1g/m2 CNS Prophylaxis Treatment Patients at high risk of CNS relapse defined by LDH > 2.5 ULN or mature B-cell disease should receive:

Methotrexate 12 mg IT in preservative-free NS (total 5 mL) day 2 Cytarabine 70 mg IT in preservative-free NS (total 5 mL) day 11 of courses A and B for a total of 16 IT injections

All other patients will receive the MTX Day 2 and cytarabine day 11 in course A only (total of 8 IT injections)

Cycle Frequency A total of 8 cycles is administered (4 x A, 4 x B) with the goal to give treatment as rapidly as possible

Dose Hematologic Toxicity Modification If absolute neutrophil count < 1.0 x 109/L or platelets < 50 x 109/L, delay Hyper-CVAD Criteria cycle

Renal Failure If Creatinine clearance = 12-48 mL/min, reduce methotrexate to 50% of initial dose If Creatinine clearance < 18 mL/min, reduce cyclophosphamide to 50% of initial dose If Creatinine clearance < 12 mL/min, omit methotrexate

Hepatic Failure If bilirubin = 25 – 50 µmol/L, reduce doxorubicin to 50% of initial dose and vincristine to 50% of initial dose If bilirubin = 40-60 µmol/L, reduce methotrexate to 75% of initial dose If bilirubin = 51 – 85 µmol/L, reduce cyclophosphamide to 75% of initial dose, doxorubicin to 25% of initial dose and vincristine to 25% of initial dose If bilirubin >60 µmol/L, omit methotrexate If bilirubin > 85 µmol/L, omit doxorubicin

Cost $835 per cycle (Parts A & B together)

References Kantarjian HM, O’Brien S, Smith TL, et al. Results of treatment with hyper-CVAD, a dose- intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol. 2000 Feb;18(3):547- 61. Abbreviations: ALL = acute lymphoblastic leukemia; IT = intrathecally; IV = intravenously; MTX = Methotrexate; NS = normal saline; p.o. = by mouth; ULN = upper limit of normal

Appendix B Page 31 of 61

Hyper-CVAD (Inpatient Orders)

Physician’s Orders

Patient Identification

Note: Extracted from the Sunnybrook Health Sciences Centre Inpatient Order Sheet Hyper-CVAD Course A Chemotherapy for High Risk ALL/Burkitt's Lymphoma YES NO Doctor must check off Yes/No for all orders Pre-chemotherapy blood work (if not done prior to admission): CBC, differential, electrolytes, blood glucose, calcium profile, liver profile, renal profile, LDH, uric acid Hold chemotherapy until a Doctor approves blood work results Daily blood work: CBC, differential, electrolytes, renal profile Allopurinol 300 mg p.o. daily (starting on day 1) for Cycle 1 only ANTIEMETIC THERAPY Ondansetron 8 mg p.o. 30 minutes prior to first dose of chemotherapy, then q12h x 7 doses Prochlorperazine 10 mg p.o./IV q4h prn for nausea or vomiting Dexamethasone 8 mg p.o. od x 3 doses, with breakfast starting on Day 5 __/__/__ (YY/MM/DD) CHEMOTHERAPY ADMINISTRATION Height:______cm Weight:______kg BSA:______m2 DAY 1 (YY/MM/DD): | | | Dexamethasone 40 mg p.o./IV with breakfast Cyclophosphamide (300 mg/m2)______mg IV in 100 mL normal saline over 3 hours q12h x 2 doses DAY 2 (YY/MM/DD): | | | Dexamethasone 40 mg p.o./IV with breakfast Cyclophosphamide (300 mg/m2)______mg IV in 100 mL normal saline over 3 hours q12h x 2 doses Preservative-free methotrexate 12 mg in normal saline (total volume of 5 mL) for intrathecal injection (to be given by Doctor) DAY 3 (YY/MM/DD): | | | Dexamethasone 40 mg p.o./IV with breakfast Cyclophosphamide (300 mg/m2)______mg IV in 100 mL normal saline over 3 hours q12h x 2 doses DAY 4 (YY/MM/DD): | | | Dexamethasone 40 mg p.o./IV with breakfast Doxorubicin (50 mg/m2)______mg IV push (12 hours after last dose of cyclophosphamide) Vincristine 2 mg IV in 50 mL of normal saline over 15 minutes DAY 11 (YY/MM/DD): | | | To be given in OCC as an outpatient (If yes, ensure follow up appointment in the chemotherapy suite is booked prior to discharge) Dexamethasone 40 mg p.o./IV daily x 4 days with breakfast on days 11 to 14 Vincristine 2 mg IV in 50 mL of normal saline over 15 minutes Cytarabine 70 mg in normal saline (total volume of 5 mL) for intrathecal injection (to be given by the Doctor) Doctor’s Signature: Date (YY/MM/DD):

Page 32 of 61 Appendix B

Hyper-CVAD (Inpatient Orders)

Physician’s Orders

Patient Identification

Note: Extracted from the Sunnybrook Health Sciences Centre Inpatient Order Sheet Hyper-CVAD Course B Chemotherapy for High Risk ALL/Burkitt's Lymphoma YES NO Doctor must check off Yes/No for all orders Patient received Hyper-CVAD Part A Prechemotherapy blood work (if not done prior to admission): CBC, differential, electrolytes, blood glucose, calcium profile, liver profile, renal profile, LDH, uric acid

Serum methotrexate levels daily (starting day 2) until methotrexate level is < 0.1µmol/L Other daily blood work: Calcium profile, electrolytes, renal profile Urine pH b.i.d. Hold chemotherapy until a Doctor approves blood work Allopurinol 300 mg p.o. daily (starting on day 1) for Cycle 1 only Sodium bicarbonate 600 mg p.o. t.i.d. (starting on day 1) Prednisolone 1% ophthalmic solution 1 drop both eyes qid x 5 days, starting on day 1 Hydration: IV D5W with 150 mmol/L sodium bicarbonate to run @ (80 mL/m2/hr) ______mL/hr starting the morning of IV methotrexate and to continue until the methotrexate level is < 0.1μmol/L Monitor intake and output daily ANTIEMETIC THERAPY Dexamethasone 12 mg p.o. 30 minutes prior to chemotherapy on days 1-3 Ondansetron 8 mg p.o. 30 minutes prior to first dose of chemotherapy, then q12h x 5 doses Dexamethasone 8 mg p.o. od x 3 doses, with breakfast, starting on Day 4 __/__/__ (YY/MM/DD) Prochlorperazine 10 mg p.o./IV q4h prn with nausea and vomiting CHEMOTHERAPY ADMINISTRATION Height:______cm Weight:______kg BSA:______m2 DAY 1 (YY/MM/DD): | | | Methotrexate (1000 mg/m2)______mg IV in 1 L normal saline to run over 24 hours DAY 2 (YY/MM/DD): | | | Folinic acid (25 mg/m2)______mg IV q6h to begin 24 hours after starting the methotrexate infusion; continue until methotrexate level is < 0.1µmol/L Cytarabine (3000 mg/m2)______mg IV in 250 mL normal saline over 2 hours q12hx 2 doses DAY 3 (YY/MM/DD): | | | Cytarabine (3000 mg/m2)______mg IV in 250 mL normal saline over 2 hours q12hx 2 doses Doctor’s Signature: Date (YY/MM/DD):

Appendix B Page 33 of 61

Hyper-CVAD (Maintenance Therapy)

Oral 6 mercaptopurine (6-MP), vincristine, methotrexate, prednisone (POMP)

6 mercaptopurine, 50 mg three times daily orally (on empty stomach) Methotrexate 20 mg/m2 orally once weekly (Round dose to nearest 2.5 mg) Vincristine, 2 mg IV, in 50mL NS over 15 minutes once monthly Prednisone 200 mg orally once daily days 1 to 5 of each month

Antibiotic prophylaxis during maintenance

Trimethoprim-sulfamethoxazole orally twice daily on weekends Acyclovir, 200 mg, or valacyclovir, 500 mg, orally once daily 3 days/week

Maintenance Therapy According to Karyotype and Immunophenotype for Hyper-CVAD in ALL

Philadelphia chromosome-positive Mature B-cell acute Others acute lymphocytic leukemia lymphocytic leukemia

↓ (Burkitt’s) ↓ Allogeneic stem cell transplantation any time in POMP therapy for 2 remission No maintenance years Or IFN + cytarabine for 2 years

Abbreviations: IFN = interferon; IV = intravenously

Page 34 of 61 Appendix B

Intravenous Immunoglobulin

Indications ITP Autoimmune hemolytic anemia Hypogammaglobulinemia

Drug Regimen Hypogammaglobulinemia 400 mg/kg/month

Other Indications 1000 mg/kg/day x 2 days

Infuse IV at 50 mL/h x 30 minutes

Increase rate as tolerated to a maximum of 300 mL/h

Cost Supplied by Canadian Blood Service and dispensed by Blood Bank. No direct cost to hospital or patient

References Anderson, D., et al., Guidelines on the use of intravenous immune globulin for hematologic conditions. Transfus Med Rev, 2007. 21(2 Suppl 1): p. S9-56.

Sunnybrook Intranet Site – access as follows: “Sunnybrook Intranet Site Homepage”, “Pharmacy Tab” Under “Pharmacy Resources” Heading click on IM, IV SC Drug Administration then click on “IV Drug Monographs” Click on “I” from the index, find Immune Globulin, Intravenous and follow link to Patient Care Policy. Direct link: http://sunnynet.ca/Default.aspx?cid=100818.

Policies and Procedures: Click on Policies and Procedures tab, click on “Patient Care” from menu then click on “Transfusion Medicine” then click on “Blood: Transfusion of Blood components and Products – Adult Patient once in document scroll down to Appendix I: IVIG Guidelines.

Abbreviations: ITP = idiopathic thrombocytopenic purpura; IV = intravenously

Appendix B Page 35 of 61

® IV Iron Replacement (Venofer )

Calculate Formula: Dose [milligrams] = (110 – Hemoglobin [g/L]) x weight [kg] x 0.22 Total Dose Most Recent Hemoglobin ______g/L

Weight ______kg

Total Dose (mg) = (110 - ______g/L) x ______kg x 0.22 = ______mg

Add 500 mg to replace iron stores

Total dose rounded to nearest 300mg = ______mg

Administer in 300 mg IV infusions over 120 minutes once weekly until total dose reached.

Example for hemoglobin of 80g/L in a patient weighing 60kg:

Dose [mg] = (110 – 80) x 60 x 0.22 = 396 mg Add 500 mg to replace iron stores = 896 mg Round up to nearest 300 mg = 900 mg Thus the patient would receive 3 x 300 mg (900 mg total dose) weekly infusions

Infusion Protocol 1. Pre-infusion vital signs 2. Insertion of intravenous 3. Infusion of iron sucrose 300 mg of iron sucrose (Venofer) in 250 cc normal saline infused over 2 hours 4. Saline lock intravenous 5. Post-infusion vital signs 6. 30 minute post-infusion observation period for adverse reactions 7. Infusion to be stopped for any adverse reactions. Most responsible physician to be notified of any adverse reactions to assess patient, and re-assess medication order 8. Tranfusionist to be notified of any serious adverse reactions (hypotension, rash, tongue or facial swelling, urticaria, pruritus, fever or any other reaction considered serious by the primary physician) 9. Intravenous removed and patient discharged home if no serious adverse reactions

Page 36 of 61 Appendix B

Lenalidomide

Indications Second-line therapy for multiple myeloma

Drug Regimen Lenalidomide 25 mg p.o. days 1-21 Dexamethasone 40 mg p.o. days 1-4, 9-12, 17-20 for cycles 1-4 Dexamethasone 40 mg p.o. days 1-4 cycles 5 onward

Cycle Frequency Repeat cycle every 28 days until signs of progression

DVT Prophylaxis Consider antiplatelet therapy with ASA 325 mg daily, or LMWH prophylaxis

Dose For grade III/IV hematologic toxicity hold lenalidomide until recovery then restart Modification at lower dose (suggest decrease to 15 mg od, then 10 mg od, then discontinue) Criteria

Cost $9240 per cycle

References Dimopoulos, M., et al., Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med, 2007. 357(21): p. 2123-32.

Abbreviations: p.o. = by mouth

Appendix B Page 37 of 61

Magrath

Indications First-line therapy for Burkitt’s lymphoma

Drug Regimen Regimen A-Codox M Cyclophosphamide 800 mg/m2 in 500 mL NS over 1 hour day 1 200 mg/m2/day in 50 mL NS over 1 hour days 2-5

Doxorubicin 40 mg/m2 IV push day 1

Vincristine 1.5 mg/m2 (maximum 2 mg) IV in 50 mL NS over 15 minutes days 1 and 8 NB: may also give day 15 in cycle 3 only if no neuropathy

Cytarabine 70 mg IT in preservative-free NS (5 mL total) days 1 and 3

Methotrexate 6720 mg/m2 day 10

Given as follows: Methotrexate 1200 mg/m IV in 1000 mL NS over 1 hour then methotrexate 5520 mg/m2 IV in 1000 mL NS as continuous infusion over 23 hours to begin immediately following the completion of the first dose of methotrexate

MTX should be administered: If creatinine clearance is > 50 cc/minute Administer MTX day 10 regardless of blood counts Stop MTX infusion after 24 hours regardless of dose given

Folinic Acid 192 mg/m2 IV 12 hours after completion of MTX infusion day 11 then 12 mg/m2 q6h thereafter until serum MTX level <0.1 µmol/L

G-CSF 300 µg sc. daily starting day 13

Methotrexate 12 mg IT in preservative-free NS (5 mL total) day 15 Regimen B-IVAC Ifosfamide 1500 mg/m2 mix with Mesna 1500mg/m2 in 1L NS over 2 hours days 1-5

Mesna 360 mg/m2 in 100 mL NS over 15 min q3h x 2 doses to begin 4 hours following the completion of the ifosfamide infusion days 1-5

Cytarabine 2000 mg/m2 in 250 mL NS over 1 hour q12h days 1 and 2

Etoposide 60 mg/m2 in 500 mL NS over 1 hour days 1-5

Methotrexate 12 mg IT in preservative-free NS (5mL total) day 5

G-CSF 300 µg sc. daily starting day 7 Patients with CNS involvement at presentation should receive intensified treatment with IT cytarabine 70 mg on days 1,3 and 5 of CODOX-M (cycle 1) and days 7 and 9 of IVAC (cycle2) supplemented by IT MTX 12 mg on days 15 and 17 of CODOX-M (cycle 1) and day 5 of IVAC (cycle 2).

Page 38 of 61 Appendix B

Magrath (cont.)

Cycle Frequency Advanced stage – alternate A + B regimens every 3 weeks for total of 4 cycles (2A & 2B) (A, B, A, B)

Limited stage – 3A cycles every 3 weeks (A, A, A)

Dose Renal Failure Modification Criteria If serum creatinine > 150 µmol/L or creatinine clearance < 0.3 ml/sec Decrease cyclophosphamide to 50% of initial dose Omit methotrexate Decrease ifosfamide to 75% of initial dose Decrease etoposide to 75% of initial dose

Hepatic Failure

If bilirubin 25-51 µmol/L or AST 60-180 IU/L Decrease doxorubicin to 75% of initial dose Decrease vincristine to 50% of initial dose Decrease etoposide to 50% of initial dose

If bilirubin 52-85 µmol/L or AST > 180 IU/L Decrease vincristine to 25% of initial dose Decrease methotrexate to 75% of initial dose Decrease etoposide to 25% of initial dose

If Bilirubin > 85 µmol/L Hold doxorubicin, methotrexate and etoposide

Cost $4800 per cycle (Parts A & B together)

References Mead, G.M., et al., An international evaluation of CODOX-M and CODOX-M alternating with IVAC in adult Burkitt's lymphoma: results of United Kingdom Lymphoma Group LY06 study. Ann Oncol, 2002. 13(8): p. 1264-74. Abbreviations: IT = intrathecally; IV = intravenously; MTX = methotrexate; NS = normal saline; sc. = subcutaneously

Appendix B Page 39 of 61

Magrath (Inpatient Orders)

Page 1/2

Physician’s Orders

Patient Identification

Note: Extracted from the Sunnybrook Health Sciences Centre Inpatient Order Sheet Magrath Regimen A-CODOX-M Chemotherapy for Burkitt's Lymphoma YES NO Doctor must check off Yes/No for all orders Pre-chemotherapy blood work (if not done prior to admission): CBC, differential, electrolytes, blood glucose, calcium profile, liver profile, renal profile, LDH, uric acid Urinalysis, electrolytes, renal profile daily on days 2-5 CBC, differential on day 8 CBC, differential, electrolytes, renal profile, calcium profile, urinalysis, urine pH on day 10 prior to chemotherapy; notify Doctor if urine pH > 7.0 Electrolytes, renal profile daily on days 11-14 CBC, differential on day 15 and daily thereafter Serum methotrexate levels daily (starting the day following methotrexate administration) until methotrexate level is < 0.1 µmol/L Hold chemotherapy until a Doctor approves blood work results Allopurinol 300 mg p.o. daily (starting on day 1) Monitor intake and output daily ANTIEMETIC THERAPY Dexamethasone 12 mg p.o. 30 minutes prior to chemotherapy on days 1-12 Ondansetron 8 mg p.o. 30 minutes prior to chemotherapy and qhs on days 1-5 and day 10 Prochlorperazine 10 mg p.o./IV q4h prn for nausea and vomiting CHEMOTHERAPY ADMINISTRATION Height:______cm Weight:______kg BSA:______m2 DAY 1 (YY/MM/DD): | | | Cyclophosphamide (800 mg/m2)______mg IV in 500 mL normal saline over 1 hour Doxorubicin (40 mg/m2)______mg IV push Vincristine (1.5 mg/m2)______mg (maximum 2 mg) IV in 50 mL of normal saline over 15 minutes Cytarabine 70 mg in normal saline (total volume of 5 mL) for intrathecal injection (to be given by the Doctor) DAY 2 (YY/MM/DD): | | | Cyclophosphamide (200 mg/m2)______mg IV in 50 mL normal saline over 1 hour Doctor’s Signature: Date (YY/MM/DD):

Page 40 of 61 Appendix B

Magrath (Inpatient Orders)

Page 2/2

Physician’s Orders

Patient Identification

Note: Extracted from the Sunnybrook Health Sciences Centre Inpatient Order Sheet Magrath Regimen A-CODOX-M Chemotherapy for Burkitt's Lymphoma YES NO Doctor must check off Yes/No for all orders DAY 3 (YY/MM/DD): | | | Cyclophosphamide (200 mg/m2)______mg IV in 50 mL normal saline over 1 hour Cytarabine 70 mg in normal saline (total volume of 5 mL) for intrathecal injection (to be given by the Doctor) DAY 4 (YY/MM/DD): | | | Cyclophosphamide (200 mg/m2)______mg IV in 50 mL normal saline over 1 hour DAY 5 (YY/MM/DD): | | | Cyclophosphamide (200 mg/m2)______mg IV in 50 mL normal saline over 1 hour DAY 8 (YY/MM/DD): | | | Vincristine (1.5 mg/m2)______mg (maximum 2 mg) IV in 50 mL of normal saline over 15 minutes DAY 10 (YY/MM/DD): | | | Hydration: IV D5W with 150 mmol/L sodium bicarbonate to run @ (80 mL/m2/hr) ______mL/hr to begin 6 hours prior to starting methotrexate; continue until methotrexate level is < 0.1µmol/L Methotrexate (1200 mg/m2)______mg IV in 1000 mL normal saline over 1 hour Methotrexate (5520 mg/m2)______mg IV in 1000 mL normal saline as continuous infusion over 23 hours to begin immediately following the completion of the first dose of methotrexate DAY 11 (YY/MM/DD): | | | Folinic acid (192 mg/m2)______mg IV 12 hours following the completion of the methotrexate infusion; then folinic Acid (12 mg/m2)______mg IV q6h; continue until methotrexate level is < 0.1 µmol/L DAY 13 (YY/MM/DD): | | | Filgrastim 300 µg sc. daily until neutrophil count is > 1.0 x 109/L DAY 15 (YY/MM/DD): | | | Preservative-free methotrexate 12 mg in normal saline (total volume of 5 mL) for intrathecal injection (to be given by the Doctor) Doctor’s Signature: Date (YY/MM/DD):

Appendix B Page 41 of 61

Magrath (Inpatient Orders)

Page 1/2

Physician’s Orders

Patient Identification

Note: Extracted from the Sunnybrook Health Sciences Centre Inpatient Order Sheet Magrath Regimen B-IVAC Chemotherapy for Burkitt's Lymphoma YES NO Doctor must check off Yes/No for all orders Prechemotherapy blood work (if not done prior to admission): CBC, differential, electrolytes, blood glucose, calcium profile, liver profile, renal profile, LDH, uric acid Daily blood work: Electrolytes, renal profile Daily urinalysis prechemotherapy; notify Doctor if hematuria is present Hold chemotherapy until a Doctor approves blood work results Allopurinol 300 mg p.o. daily (starting on day 1) ANTIEMETIC THERAPY Dexamethasone 12 mg p.o. 30 minutes prior to chemotherapy on days 1-5 Ondansetron 8 mg p.o. 30 minutes prior to first dose of chemotherapy, then q12h x 9 doses Dexamethasone 8 mg p.o. od x 3 doses, with breakfast starting on day 6 Prochlorperazine 10 mg p.o./IV q4h prn for nausea and vomiting CHEMOTHERAPY ADMINISTRATION Height:______cm Weight:______kg BSA:______m2 DAY 1 (YY/MM/DD): | | | Ifosfamide (1500 mg/m2)______mg IV mixed with mesna (1500 mg/m2)______mg IV in 1000 mL normal saline over 2 hours Mesna (360 mg/m2)______mg IV in 100 mL normal saline over 15 minutes q3h x 2 doses to begin 4 hours following the completion of the ifosfamide infusion Cytarabine (2000 mg/m2) ______mg IV in 250 mL normal saline over 1 hour q12h x 2 doses Etoposide (60 mg/m2)______mg IV in 500 mL normal saline over 1 hour with in-line filter DAY 2 (YY/MM/DD): | | | Ifosfamide (1500 mg/m2)______mg IV mixed with mesna (1500 mg/m2)______mg IV in 1000 mL normal saline over 2 hours Mesna (360 mg/m2)______mg IV in 100 mL normal saline over 15 minutes q3h x 2 doses to begin 4 hours following the completion of the ifosfamide infusion Cytarabine (2000 mg/m2) ______mg IV in 250 mL normal saline over 1 hour q12h x 2 doses Etoposide (60 mg/m2)______mg IV in 500 mL normal saline over 1 hour with in-line filter Doctor’s Signature: Date (YY/MM/DD):

Page 42 of 61 Appendix B

Magrath (Inpatient Orders)

Page 2/2

Physician’s Orders

Patient Identification

Note: Extracted from the Sunnybrook Health Sciences Centre Inpatient Order Sheet Magrath Regimen B-IVAC Chemotherapy for Burkitt's Lymphoma YES NO Doctor must check off Yes/No for all orders DAY 3 (YY/MM/DD): | | | Ifosfamide (1500 mg/m2)______mg IV mixed with mesna (1500 mg/m2)______mg IV in 1000 mL normal saline over 2 hours Mesna (360 mg/m2)______mg IV in 100 mL normal saline over 15 minutes q3h x 2 doses to begin 4 hours following the completion of the ifosfamide infusion Etoposide (60 mg/m2)______mg IV in 500 mL normal saline over 1 hour with in-line filter DAY 4 (YY/MM/DD): | | | Ifosfamide (1500 mg/m2)______mg IV mixed with mesna (1500 mg/m2)______mg IV in 1000 mL normal saline over 2 hours Mesna (360 mg/m2)______mg IV in 100 mL normal saline over 15 minutes q3h x 2 doses to begin 4 hours following the completion of the ifosfamide infusion Etoposide (60 mg/m2)______mg IV in 500 mL normal saline over 1 hour with in-line filter DAY 5 (YY/MM/DD): | | | Ifosfamide (1500 mg/m2)______mg IV mixed with mesna (1500 mg/m2)______mg IV in 1000 mL normal saline over 2 hours Mesna (360 mg/m2)______mg IV in 100 mL normal saline over 15 minutes q3h x 2 doses to begin 4 hours following the completion of the ifosfamide infusion Etoposide (60 mg/m2)______mg IV in 500 mL normal saline over 1 hour with in-line filter Preservative-free methotrexate 12 mg in normal saline (total volume of 5 mL) for intrathecal injection (to be given by the Doctor) DAY 7 (YY/MM/DD): | | | Filgrastim 300 µg sc. daily until neutrophil count is > 1 x 109/L Doctor’s Signature: Date (YY/MM/DD):

Appendix B Page 43 of 61

Melphalan + Prednisone

Indications First-line therapy for multiple myeloma (non-transplant candidate)

Drug Regimen Melphalan 9 mg/m2 /day p.o. days 1-4 (round off to nearest 2 mg) Prednisone 100 mg/day p.o. days 1-4

Cycle Frequency Repeat every 28 days until plateau or 1 year

Dose Hematologic Toxicity Modification Day 15 if platelet > 100 x 109/L or absolute neutrophil count > 1.0 x 109/L, or Criteria platelets > 75 x 109/L; increase does of melphalan by 3 mg/m2/day

Day 28 if platelets < 100 x 109/L or absolute neutrophil count < 1.0 x 109/L; delay 1 week and decrease dose of melphalan by 3 mg/m2/day

Renal Failure If serum creatinine > 265 µmol/L, reduce melphalan dose by 3 mg/m2/day

Cost < $100 per cycle (patient cost)

References Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. Myeloma Trialists' Collaborative Group. J Clin Oncol, 1998. 16(12): p. 3832-42.

Abbreviations: p.o. = by mouth

Page 44 of 61 Appendix B

MPT

Indications First-line therapy for multiple myeloma in non-transplant eligible patients

Drug Regimen Melphalan 9 mg/m2/day p.o. days 1-4 Prednisone 100 mg/day p.o. days 1-4 Thalidomide 100 mg/day p.o. continuously

Thalidomide (maintenance) 100 mg/day p.o. until progression or toxicity

Cycle Frequency Repeat every 28 days until nadir (6 to maximum – 12 cycles)

Dose Hematologic Toxicity Modification If platelets > 100 x 109/L, absolute neutrophil count on day 15 > 0.5 x 109/L and Criteria absolute neutrophil count on day 29 > 1.0 x 109/L; increase dose of melphalan by 3 mg/m2/day

If platelets < 100 x 109/L or absolute neutrophil count < 1.0 on day 29, delay 1 week and decrease dose of melphalan by 3 mg/m2/day

Renal Failure If serum creatinine > 265 µmol/L, reduce melphalan dose by 3 mg/m2/day

Nonhematologic toxicity of thalidomide – ex-peripheral neuropathy /constipation /somnolence

If patients exhibit grade III or IV nonhematologic toxicity to thalidomide – decrease thalidomide by 50%

Cost < $100 per cycle (patient costs) Currently thalidomide access via Special Access Program and CANTAP Compassionate Access Program

References Palumbo, A., et al., Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet, 2006. 367(9513): p. 825-31.

Abbreviations: p.o. – by mouth

Appendix B Page 45 of 61

MPV

Indications Therapy for newly diagnosed multiple myeloma in the elderly

Drug Regimen Premedications Ondansetron 8 mg p.o. and Stemetil 10 mg p.o. q4h prn.

Melphalan 9 mg/m2 days 1-4 Prednisone 60 mg/m2 (cap at 100 mg) days 1-4 Velcade 1.3 mg/m2 days 1, 4, 8, 11, 22, 25, 29, 32 (cycles 1-4) Velcade 1.3 mg/m2 days 1, 8, 22, 29 (cycles 5-9)

Cycle Frequency 6 weeks x 9 cycles

Dose Velcade Dose Adjustments Modification Withhold therapy at the onset of any grade 3 non-hematological or grade 4 Criteria hematological toxicities, excluding neuropathy discussed in the following dose modification section. Once symptoms of toxicity have resolved, reinitiate therapy at a 25% dose reduction (e.g. 1.3 mg/m2 /dose reduced to 1 mg/m2 /dose).

There is no dose modification for grade 1 peripheral neuropathy (paresthesias and/or loss of reflexes) without pain or loss of function. For grade 1 peripheral neuropathy with pain or grade 2 (interfering with function, but not with activities of daily living), reduce dose to 1 mg/m 2. For grade 2 peripheral neuropathy with pain or grade 3 (interfering with activities of daily living), withhold therapy until toxicity resolves, then reinitiate therapy with a reduced dose of 0.7 mg/m2 and change treatment schedule to once weekly. Discontinue therapy for grade 4 (permanent sensory loss that interferes with function).

Cost ~ $10,000 per cycle

References San Miguel, J.F., et al., Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med, 2008. 359(9): p. 906-17.

Page 46 of 61 Appendix B

Mini-BEAM

Indications Salvage therapy of Hodgkin’s and non-Hodgkin’s lymphoma

Drug Regimen Carmustine 60 mg/m2 IV in 250 mL NS over 90 minutes day 1 Etoposide (VP-16) 75 mg/m2 IV in 500 mL NS over 45 minutes days 2, 3, 4, 5 Cytarabine 100 mg/m2 sc.q12h days 2, 3, 4, 5 Melphalan 30 mg/m2 IV in 100 mL NS over 20 minutes (round off to nearest 50 mg dose) day 6

Cycle Frequency Every 4-6 weeks

Dose Hematologic Toxicity Modification No dose reductions, consider prophylactic filgrastim Criteria Cost $530 per cycle

References Stewart AK, Brandwein JM, Sutcliffe SB, Scott JG and Keating A. Mini-Beam as salvage chemotherapy for refractory Hodgkin’s disease and non-Hodgkin’s lymphomas. Leuk Lymphoma 1991:5; 111-115.

Abbreviations: IV = intravenously; NS = normal saline; sc. = subcutaneously

Appendix B Page 47 of 61

Mini-BEAM (Inpatient Orders)

Physician’s Orders

Patient Identification

Note: Extracted from the Sunnybrook Health Sciences Centre Inpatient Order Sheet Mini-BEAM Salvage Chemotherapy for Hodgkin's & Non-Hodgkin's Lymphoma YES NO Doctor must check off Yes/No for all orders Prechemotherapy blood work (if not done prior to admission): CBC, differential, electrolytes, blood glucose, calcium profile, liver profile, renal profile, LDH, uric acid Hold chemotherapy until a Doctor approves blood work results ANTIEMETIC THERAPY Dexamethasone 12 mg p.o. 30 minutes prior to chemotherapy on days 1-6 Ondansetron 8 mg p.o. 30 minutes prior to first dose of chemotherapy, then q12h x 11 doses Dexamethasone 8 mg p.o. od x 3 doses, with breakfast, starting on day 7 /__/__/__(YY/MM/DD) Prochlorperazine 10mg p.o./IV q4h prn for nausea and vomiting CHEMOTHERAPY ADMINISTRATION Height:______cm Weight:______kg BSA:______m2 DAY 1 (YY/MM/DD): | | | Carmustine (60 mg/m2)______mg IV in 250 mL NS over 90 minutes with non PVC tubing DAY 2 (YY/MM/DD): | | | Etoposide (75 mg/m2)______mg IV in 500 mL of normal saline over 45 minutes with in-line filter Cytarabine (100 mg/m2)______mg sc. q12h x 2 doses DAY 3 (YY/MM/DD): | | | Etoposide (75 mg/m2)______mg IV in 500 mL of normal saline over 45 minutes with in-line filter Cytarabine (100 mg/m2)______mg sc., q12h x 2 doses DAY 4 (YY/MM/DD): | | | Etoposide (75 mg/m2)______mg IV in 500 mL of normal saline over 45 minutes with in-line filter Cytarabine (100 mg/m2)______mg sc. q12h x 2 doses DAY 5 (YY/MM/DD): | | | Etoposide (75 mg/m2)______mg IV in 500 mL of normal saline over 45 minutes with in-line filter Cytarabine (100 mg/m2)______mg sc. q12h DAY 6 (YY/MM/DD): | | | Melphalan (30 mg/m2)______mg IV in 100 mL of normal saline over 20 minutes Doctor’s Signature: Date (YY/MM/DD):

Page 48 of 61 Appendix B

MOPP

Indications Therapy for Hodgkin’s lymphoma (not typically first-line)

Drug Regimen Mechlorethamine 6 mg/m2 IV push days 1 and 8

Vincristine 1.4 mg/m2 (maximum 2 mg) IV in 50 mL NS over 15 minutes days 1 & 8

Procarbazine 100 mg/m2 p.o. daily (round off to nearest 50 mg) days 1-14

Prednisone 50 mg/m2 p.o. daily (cycles 1 & 4 only) days 1-14

Cycle Frequency Repeat every 28 days (usual total 6 cycles)

Dose Hematologic Toxicity Modification Hold dose for 1 week if absolute neutrophil count < 1.0 x 109/L or platelets < 75 x Criteria 109/L

Filgrastim support should be considered after first episode of febrile neutropenia or dose delay ≥ 1 week

Renal Failure Consider dose reduction of procarbazine if serum creatinine > 150 μmol/L

Hepatic Dysfunction If bilirubin = 25-50 μmol/L or AST = 60-180 IU/L reduce vincristine to 50% dose of initial dose

If bilirubin > 50 μmol/L or AST > 180 IU/L, reduce vincristine to 25% dose of initial dose

Cost $50 per cycle

References Devita, V.T., Jr., A.A. Serpick, and P.P. Carbone, Combination chemotherapy in the treatment of advanced Hodgkin's disease. Ann Intern Med, 1970. 73(6): p. 881-95.

Abbreviations: IV = intravenously; NS = normal saline; p.o. – by mouth

Appendix B Page 49 of 61

NOVE

Indications Consolidation for AML (age > 60)

Drug Regimen Mitoxantrone 10 mg/m2 IV push daily days 1-5 Etoposide (VP-16) 100 mg/m2 IV in 500 mL NS over 1 hour days 1-5

Cycle Frequency One cycle only

Dose Hematologic Toxicity Modification If absolute neutrophil count < 1.0 x 109/L or platelets < 75 x 109/L delay Criteria consolidation

Hepatic Dysfunction If bilirubin 26 – 51 µmol/L or AST 60 – 180 IU/L, reduce mitoxantrone to 75% of initial dose

If bilirubin 52 – 80 µmol/L or AST > 180 IU/L, reduce mitoxantrone to 50% of initial dose

If bilirubin > 85 µmol/L omit mitoxantrone

Cost $1062.50 per cycle

Abbreviations: AML – acute myelogenous leukemia; IV = intravenously; NS = normal saline

Page 50 of 61 Appendix B

NOVE-HIDAC

Indications Second-line induction therapy for AML (age > 60)

Drug Regimen Mitoxantrone 10 mg/m2 IV push daily days 1-5

Etoposide (VP-16) 100 mg/m2 IV in 500 mL NS over 1 hour days 1-5

Cytarabine (ARA-C) 1500* mg/m2 IV in 250 mL NS over 3 hours x 4 doses days 6 and 7

*For patients aged >60 years reduce cytarabine dose to 1000 mg/m2

Cycle Frequency One cycle only

Dose Hematologic Toxicity Modification If absolute neutrophil count < 1.0 x 109/L or platelets < 75 x 109/L delay Criteria consolidation

Hepatic Dysfunction If bilirubin 26 – 51 µmol/L or AST 60 – 180 IU/L, reduce mitoxantrone to 75% of initial dose

If bilirubin 52 – 80 µmol/L or AST > 180 IU/L, reduce mitoxantrone to 50% of initial dose

If bilirubin > 85 µmol/L omit mitoxantrone

Cost $1674.50 per cycle

Abbreviations: AML – acute myelogenous leukemia; IV = intravenously; NS = normal saline

Appendix B Page 51 of 61

POMP Maintenance

Indications Maintenance oral chemotherapy for acute lymphoblastic leukemia/lymphoma

Drug Regimen Mercaptopurine 50 mg p.o. t.i.d. daily Methotrexate 20 mg p.o. once weekly Vincristine 2 mg IV day 1 Prednisone 20o mg p.o. od days 1-5

PCP Prophylaxis Septra® 1 double strength tablet 3 times per week

Herpes & Varicella Prophylaxis Acyclovir 200 mg p.o. daily Or valacyclovir 500 mg p.o. daily

Cycle Frequency Repeat cycle every 28 days To complete 2 full years of chemotherapy from the start of induction treatment

Cost $450 per cycle

References Kantarjian, H.M., et al., Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol, 2000. 18(3): p. 547- 61.

Green, H., et al., Prophylaxis of Pneumocystis pneumonia in immunocompromised non-HIV-infected patients: systematic review and meta- analysis of randomized controlled trials. Mayo Clin Proc, 2007. 82(9): p. 1052-9.

Page 52 of 61 Appendix B

Rituximab

Indications Salvage therapy for follicular and low-grade lymphoma

Drug Regimen Premedications Acetaminophen 1000 mg p.o. and diphenhydramine 50 mg IV prior to rituximab

Rituximab 375 mg/m2 IV in 500 mL NS weekly x 4 (Note: begin infusion at 50 mg/hour, if no infusion related reactions are experienced by the patient escalate by 50 mg/hour every 30 minutes to a maximum of 400 mg/hour)

Cycle Frequency 4 weekly infusion

Cost $11,000 per 4-week treatment

References Davis, T.A., et al., Single-agent monoclonal antibody efficacy in bulky non- Hodgkin's lymphoma: results of a phase II trial of rituximab. J Clin Oncol, 1999. 17(6): p. 1851-7.

Abbreviations: IV = intravenously; NS = normal saline; p.o. = by mouth

Appendix B Page 53 of 61

Thalidomide / Dexamethasone

Indications First-line therapy for multiple myeloma in patients eligible for autologous stem cell transplant

Drug Regimen Thalidomide 200 mg p.o. od continuously Dexamethasone 40 mg p.o. day 1-4, 9-12, 17-20 cycles 1-4 Dexamethasone 40 mg p.o. day 1-4 cycles 5 and onward

DVT Prophylaxis Consider antiplatelet therapy with ASA 325 mg daily, or LMWH prophylaxis

Cycle Frequency Repeat cycle every 28 days 4-6 cycles (pre-autologous transplant)

Dose Non-hematologic toxicity grade III/IV ex-neuropathy/GI toxicity 50% dose Modification reduction Criteria Cost < $100 per cycle patient’s cost

References Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. Rajkumar S.V., JCO 2008, May 1; 26(13); 2171-7.

Abbreviations: ASA = aspirin; LMWH = low molecular weight heparin; p.o. = by mouth

Page 54 of 61 Appendix B

® Vidaza

Indications High risk or high intermediate risk MDS or patients with low or low-intermediate risk MDS who are transfusion dependent and have failed growth factors or other therapies

Drug Regimen Premedications Ondansetron 8 mg p.o.

Vidaza® The recommended starting dose for the first treatment cycle, for all patients regardless of baseline hematology laboratory values, is 75 mg/m2 subcutaneously or intravenously, daily for 7 days

Subcutaneous Vidaza® suspension is administered subcutaneously. Doses Injection greater than 4 mL should be divided equally into 2 syringes Instructions and injected into 2 separate sites. Rotate sites for each injection (thigh, abdomen, or upper arm). New injections should be given at least one inch from an old site and never into areas where the site is tender, bruised, red, or hard.

Post-medications Stemetil 10 mg p.o. q4h prn x 7 days

Cycle Frequency Cycles should be repeated every 4 weeks. It is recommended that patients be treated for a minimum of 4 to 6 cycles. However, complete or partial response may require additional treatment cycles. Treatment may be continued as long as the patient continues to benefit.

Dose Adjustment for Renal Function Modification Vidaza® and its metabolites are primarily excreted by the kidney. Patients with Criteria renal impairment may be subject to increased toxicity. If unexplained elevations of BUN or serum creatinine occur, the next cycle should be delayed until values return to normal or baseline and the dose should be reduced by 50% on the next treatment course.

Dose Adjustment Based on Hematology Laboratory Values If patients do not achieve baseline ANC or platelet counts by day 29 of each cycle, possibilities for action include delay by 1-2 weeks, Neupogen or dose reduction. Most hematologic toxicities occur within the first two cycles and there is evidence that remethylation occurs by week 4. Adherence as close to the q4 week schedule is advisable unless patients are experiencing excessive hematology or nonhematologic toxicities.

Cost $6,500 per cycle

References Silverman, L.R., et al., Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol, 2002. 20(10): p. 2429-40.

Fenaux, P., et al., Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol, 2009. 10(3): p. 223-32.

Abbreviations: ANC = absolute neutrophil count; BUN = blood, urea, nitrogen; p.o. = by mouth

Appendix B Page 55 of 61

VP-16/Melphalan

Indications High-dose therapy for lymphoma (Transplant Protocol)

Drug Regimen Etoposide (VP-16) 60 mg/kg IV (undiluted) over 8 hours day –4

Melphalan 180 mg/m2 IV in 100mL NS over 30 minutes day –3

Stem Cell Infusion day 0

Cycle Frequency Single course only

Cost $1700 for single course

Abbreviations: IV = intravenously; NS = normal saline

Page 56 of 61 Appendix B

VP-16/Melphalan (Inpatient Orders)

Page 1/2

Physician’s Orders

Patient Identification

Note: Extracted from the Sunnybrook Health Sciences Centre Inpatient Order Sheet Peripheral Blood Stem Cell Transplant - Melphalan/Etoposide Protocol YES NO Doctor must check off Yes/No for all orders Admit to Dr. Date: Diagnosis: Diet: Dietitian Consult Vital signs q4h while awake, record on transplant chart Daily weight before breakfast on same scale Record intake and output on transplant chart q8h INVESTIGATIONS CBC, differential, PT/PTT, electrolytes, renal profile, liver profile, calcium profile, LDH on admission Daily CBC, differential, electrolytes, renal profile Tuesday and Friday- blood group and screen, PT/PTT, liver profile, calcium profile Draw all blood via central venous catheter by 06:30 (Draw PT/PTT from the line with the IV running to prevent distortion of results by heparin in capped apheresis line) ECG on admission Chest x-ray (PA and LAT) on admission ANTIEMETIC THERAPY Dexamethasone 4mg IV/p.o. with breakfast, lunch, dinner and at bedtime daily beginning prior to first dose of chemotherapy on Day (–4) x9 doses Ondansetron 8 mg IV/p.o. beginning prior to first dose of chemotherapy on Day (–4) and then q 8h after x12 doses, to be reassessed Day (0) Prochlorperazine 10 mg IV/p.o. q 4-6h prn for nausea or vomiting HIGH-DOSE CHEMOTHERAPY ADMINISTRATION Height:______cm Weight:______kg BSA:______m2 DAY –4 (YY/MM/DD): | | | IV normal saline with 4 mmol/L magnesium sulphate + 20 mmol/L KCl at: 200 mL/hr x 6h prior to etoposide (should be started by 5:00am) 250 mL/hr during etoposide 200 mL/hr x 96h following completion of etoposide (until Day 0) 75 mL/hr post transplant Etoposide (60mg/kg)____mg IV by continuous infusion over 8 h (undiluted solution) Doctor’s Signature: Date (YY/MM/DD):

Appendix B Page 57 of 61

VP-16/Melphalan (Inpatient Orders)

Page 2/2

Physician’s Orders

Patient Identification

Sodium bicarbonate mouthwash 2.5 mL in 100 mL of H2O q2h while awake Lorazepam 1-2 mg p.o. qhs prn for anxiety or insomnia Lidocaine 2% viscous oral solution 5-10 mL p.o. swish and spit q4h prn for mucositis Codeine 30-60 mg p.o. q4h prn for mucositis pain Ranitidine 150 mg p.o. b.i.d. DAY –3 (YY/MM/DD): | | | Melphalan (180 mg/m2)______mg IV in 100 mL normal saline to run over 30 minutes. Use dedicated line (do not y sited with hydration) (must be used within 2 hours of preparation) DAY –2 (YY/MM/DD): | | | No Chemotherapy Continue hydration at previous rate DAY –1 (YY/MM/DD): | | | Continue hydration at previous rate DAY 0 (YY/MM/DD): | | | Stem Cell Infusion DAY +1 (YY/MM/DD): | | | Nystatin suspension 500,000 U/5 mL p.o. q.i.d. swish and swallow Filgrastim (GCSF) (5 µg/kg)______µg (to be rounded to the nearest standard dose- 300 µg or 480 µg) subcutaneous daily until neutrophils >1 FEBRILE NEUTROPENIA PROTOCOL Orders 33 through to 42 should only to be initiated when neutrophils < 1 and temp >38.0oC Blood Cultures - peripheral and from all lumens of the central venous catheter Chest x-ray Urine sample for culture and sensitivity Swab all central venous catheter exit sites Doctor to assess patient and IV rate Start tobramycin (7 mg/kg)______mg (rounded to the nearest 50mg) in 100 mL D5W IV over 30 minutes q24h Tobramycin levels 30 minutes (peak) and 8 - 12 hours (random) post first dose Start cefazolin 1 gm in 50 mL D5W IV over 15-30 minutes q8h Notify Infectious disease service of febrile neutropenia in transplant patient Notify Pharmacy when patient develops febrile neutropenia Doctor’s Signature: Date (YY/MM/DD):

Page 58 of 61 Appendix B

VP-16/Prednisone

Indications Palliative therapy for lymphoma

Drug Regimen Etoposide (VP-16) 50 mg/day p.o. days 1-14 Prednisone 50 mg/day p.o. every 2 days - days 1-28

Cycle Frequency Repeat every 28 days until symptoms controlled

Dose Hematologic Toxicity Modification Decrease duration of etoposide to 7-10 days if absolute neutrophil count < 1.0 x Criteria 109/L or platelets < 75 x 109/L

Growth factor support not routinely indicated

Cost ~ $500 per cycle (patient cost)

Abbreviations: p.o. = orally

Appendix B Page 59 of 61

7 + 3 Induction

Indications Induction of AML

Drug Regimen If patient ≤ 60 years Daunorubicin 60 mg/m2 IV push days 1, 2, 3

Cytarabine 1400 mg/m2 IV in 100 mL casette of normal saline to run at 0.6 mL/hour continuous infusion via CADD pump days 1-7 (200 mg/m2/day x 7 days) If patient > 60 years Daunorubicin 60 mg/m2 IV push days 1, 2, 3

Cytarabine 700 mg/m2 IV in 100 mL casette of normal saline to run at 0.6 mL/hour continuous infusion via CADD pump days 1-7 (100 mg/m2/day x 7 days)

Cycle Frequency 1 induction only

Dose Hematologic Toxicity Modification None proceed at full dose Criteria Hepatic Failure If bilirubin = 26 – 51 µmol/L or AST = 60 – 180 IU/L reduce daunorubicin to 75% of initial dose

If bilirubin = 52 – 85 µmol/L or AST > 180 IU/L reduce daunorubicin to 50% of initial dose

If bilirubin > 85 µmol/L, omit daunorubicin

Cost $1250

References Wiernik PH. Acute leukemias in Cancer. Principals & Practice of Oncology (3rd Edition), Chapter 52, pp 1809-1835. Lippincott Press 1985.

Abbreviations: AML – Acute myelogenous leukemia; IV = intravenously

Page 60 of 61 Appendix B

7+3 Induction (Inpatient Orders)

Physician’s Orders

Patient Identification Note: Extracted from the Sunnybrook Health Sciences Centre Inpatient Order Sheet 7 + 3 Induction - Chemotherapy for Acute Myelogenous Leukemia YES NO Doctor must check off Yes/No for all orders Prechemotherapy blood work (if not done prior to admission): CBC, differential, electrolytes, blood glucose, calcium profile, liver profile, renal profile, LDH, uric acid DO NOT HOLD chemotherapy until blood work available Monitor intake and output daily ANTIEMETIC THERAPY Ondansetron 8 mg p.o. 30 minutes prior to first dose of chemotherapy, then q12h x 5 doses Dexamethasone 10 mg IV 30 minutes prior to chemotherapy on days 1-3 Dexamethasone 4 mg p.o. q12h x 6 doses, starting on day 4 Prochlorperazine 10 mg p.o./IV q.i.d. prn (for nausea) CHEMOTHERAPY ADMINISTRATION Height:______cm Weight:______kg BSA:______m2 DAY 1 (YY/MM/DD): | | | Daunorubicin (60 mg/m2) ______mg IV push Cytarabine (700 mg/m2) ______mg IV in 100 mL cassette of normal saline to run @ 0.6 mL/hr continuous infusion via CADD pump over 7 days (For patients aged <60 years old change cytarabine to 1400 mg/m2) DAY 2 (YY/MM/DD): | | | Daunorubicin (60 mg/m2) ______mg IV push DAY 3 (YY/MM/DD): | | | Daunorubicin (60 mg/m2) ______mg IV push Doctor’s Signature: Date (YY/MM/DD):

Appendix B Page 61 of 61