APPENDIX B

SUPPORTIVE CARE

1-4 ACUTE EMESIS PROPHYLAXIS o Dolasetron 100 mg and 20 mg given PO 30 minutes before Minimally Emetogenic Regimes (< 10%) chemotherapy • Prophylactic antiemetic therapy generally is not 0.25 mg IV (day 1 only) required. o and dexamethasone 20 mg PO given 30 • If the patient experiences or , minutes before use prophylactic therapy prior to subsequent Patients who do not respond to a 2-drug treatments. • combination may benefit from the following:  One of the following regimens is recommended:  A corticosteroid, antagonist, and  Dexamethasone 8 to 20 mg PO, given 30 antagonist regimen or minutes before chemotherapy  Addition of a neurokinin antagonist to their  10 mg PO ± previous regimen. 25 to 50 mg PO if needed, given 30 minutes before chemotherapy  0.5 to 2 mg/kg PO ± Mildly Emetogenic Regimens (10% to 30%) diphenhydramine 25 to 50 mg PO if needed, • For most patients, prophylactic therapy, given 30 minutes before chemotherapy particularly with a serotonin antagonist, generally is  25 to 50 mg PO ± not required. diphenhydramine 25 to 50 mg PO if needed, • If needed, one of the following regimens may be given 30 minutes before chemotherapy given 30 minutes prior to therapy: • If patient still experiences significant nausea  Dexamethasone 8 to 20 mg PO, given 30 or vomiting, add an agent from a different minutes before chemotherapy pharmacologic category to the previous  Prochlorperazine 10 mg orally ± prophylactic antiemetic regimen. diphenhydramine 25 to 50 mg PO if needed,  The following regimens are recommended: given 30 minutes before chemotherapy  Patients who received a corticosteroid only:  Metoclopramide 0.5 to 2 mg/kg PO ± Add a dopamine antagonist. diphenhydramine 25 to 50 mg PO if needed,  Patients who received a dopamine given 30 minutes before chemotherapy antagonist only: Add a corticosteroid.  Promethazine 25 to 50 mg PO ±  Patients who received a corticosteroid and diphenhydramine 25 to 50 mg PO if needed, dopamine antagonist: Substitute a serotonin given 30 minutes before chemotherapy antagonist for the dopamine antagonist. • If patient still experiences significant nausea  If a corticosteroid and dopamine antagonist or vomiting, add an agent from a different combination is not effective, a serotonin pharmacologic category to the previous antagonist and corticosteroid combination may prophylactic antiemetic regimen. be required.  The following regimens are recommended:  The following regimens are recommended:  Patients who received a corticosteroid only: o 8 to 16 mg and Add a dopamine. dexamethasone 20 mg given PO 30  Patients who received a dopamine minutes before chemotherapy antagonist only: Add a corticosteroid. o 1 to 2 mg and  Patients who received a corticosteroid and dexamethasone 20 mg given PO 30 dopamine antagonist: Substitute a serotonin minutes before chemotherapy antagonist for the dopamine antagonist. 518 Appendix B 519

 If a corticosteroid and dopamine antagonist mg PO, and 125 mg given PO combination is not effective, a serotonin 30 minutes before chemotherapy antagonist and corticosteroid combination may o Palonosetron 0.25 mg IV (day 1 only), be required. dexamethasone 12 mg, and aprepitant  The following regimens are recommended: 125 mg given PO 30 minutes before chemotherapy o Ondansetron 8 to 16 mg and dexamethasone 20 mg given PO 30 • Antiemetic therapy should continue for at least 3 minutes before chemotherapy days.  Prolonged (more than 24 hours) use of o Granisetron 1 to 2 mg and dexamethasone 20 mg given PO 30 serotonin antagonists is NOT recommended.6 minutes before chemotherapy  A corticosteroid or corticosteroid and dopamine antagonist combination is recommended for o Dolasetron 100 mg and dexamethasone 20 mg given PO 30 minutes before follow-up therapy.6 chemotherapy  One of the following regimens is suggested:  Dexamethasone 4 mg PO twice a day for 3 o Palonosetron 0.25 mg IV (day 1 only) and dexamethasone 20 mg PO given 30 days ± metoclopramide 0.5 to 2 mg/kg PO minutes before chemotherapy every 4 to 6 hours ± diphenhydramine 25 to • Patients who do not respond to a 2-drug 50 mg PO every 6 hours if needed, starting combination may benefit from the following: on day 2 of chemotherapy  A corticosteroid, dopamine antagonist, and  Dexamethasone 4 mg PO twice a day for 3 serotonin antagonist regimen or days ± prochlorperazine 10 mg PO every 4  Addition of a neurokinin antagonist to their to 6 hours ± diphenhydramine 25 to 50 mg previous regimen. PO every 6 hours if needed, starting on day 2 of chemotherapy Moderately Emetogenic Regimens (30% to 90%)  Dexamethasone 4 mg PO twice a day for 3 • Prophylactic antiemetic therapy with a serotonin days ± promethazine 25 to 50 mg PO every antagonist is recommended but may not be 4 to 6 hours ± diphenhydramine 25 to 50 mg required in all patients. PO every 6 hours if needed, starting on day 2 • One of the following regimens may be given 30 of chemotherapy minutes prior to therapy:  If a neurokinin antagonist is used, one of the  Ondansetron 8 to 24 mg PO and following regimens are suggested: dexamethasone 20 mg PO, given 30 minutes  Ondansetron 16 to 24 mg, dexamethasone before chemotherapy 12 mg, and aprepitant 125 mg given PO 30  Granisetron 1 to 2 mg PO and dexamethasone minutes before chemotherapy 20 mg PO, given 30 minutes before  Granisetron 1 to 2 mg, dexamethasone 12 chemotherapy mg, and aprepitant 125 mg given PO 30  Dolasetron 100 mg PO and dexamethasone 20 minutes before chemotherapy mg PO, given 30 minutes before chemotherapy  Dolasetron 100 mg, dexamethasone 12 mg,  Palonosetron 0.25 mg IV and dexamethasone and aprepitant 125 mg given PO 30 minutes 20 mg PO, given 30 minutes before before chemotherapy chemotherapy on day 1 only  Palonosetron 0.25 mg IV (day 1 only),

 Use of a neurokinin (NK1) antagonist is dexamethasone 12 mg, and aprepitant recommended for regimens that include both 125 mg given PO 30 minutes before doxorubicin and cyclophosphamide.2,3,5 chemotherapy  The following regimens are suggested:  Patients who experience significant nausea o Ondansetron 8 to 24 mg, dexamethasone or vomiting with one of these regimens 12 mg, and aprepitant 125 mg given PO should receive an agent from a different 30 minutes before chemotherapy pharmacologic category. o Granisetron 1 to 2 mg, dexamethasone  Substituting granisetron for ondansetron 12 mg, and aprepitant 125 mg given PO in subsequent treatment cycles has not 30 minutes before chemotherapy been shown to be effective and is NOT 7-11 o Dolasetron 100 mg, dexamethasone 12 recommended. 520 A Guide to Combination Cancer Chemotherapy Regimens

Highly Emetogenic Regimes (>90%) if needed, ± diphenhydramine 25 to 50 mg PO • Day 1 of each cycle every 6 hours if needed  serotonin antagonist  Prochlorperazine 25 mg rectally every 4 to 6

 neurokinin (NK1) antagonist hours if needed, ± diphenhydramine 25 to 50  corticosteroid mg PO every 4 to 6 hours if needed • Days 2 and 3 of each cycle  Promethazine 25 to 50 mg PO every 4 to 6  neurokinin antagonist hours if needed, ± diphenhydramine 25 to 50  corticosteroid mg PO every 4 to 6 hours if needed  ± a dopamine or serotonin antagonist • Recommended regimens SPECIAL CONSIDERATIONS  Day 1 Serotonin (5HT ) antagonists  Aprepitant 125 mg, dexamethasone 12 mg, 3 • Meta-analysis recommends against use of these and ondansetron 16 to 24 mg PO 30 minutes agents after the first 24 hours.6 before chemotherapy • There is no benefit to using granisetron in patients  Aprepitant 125 mg, dexamethasone 12 mg, who do not respond to ondansetron.7-11 and granisetron 2 mg PO 30 minutes before • High-dose granisetron (3 mg IV or 40 to 240 chemotherapy mcg/kg)7-11 for breakthrough nausea provides no  Aprepitant 125 mg, dexamethasone 12 benefit.7-11 mg, and dolasetron 100 to 200 mg PO 30 minutes before chemotherapy Carboplatin  Aprepitant 125 mg, dexamethasone 12 mg, • Causes delayed nausea or emesis similar to and palonosetron 0.5 mg PO 30 minutes cisplatin. before chemotherapy  Mechanism of action and clinical course differ 12,13  Days 2 to 3 from cisplatin.  A neurokinin antagonist and corticosteroid  Urinary 5-hydroxyindole acetic acid (5-HIAA) or neurokinin antagonist, corticosteroid, and excretion indicates carboplatin causes dopamine antagonist combination is most  A lower peak level. appropriate for follow-up therapy. One of the  Prolonged release of serotonin. following regimens is recommended: • The clinical course of nausea or vomiting  Reflects this pattern of serotonin release. o Aprepitant 80 mg PO and dexamethasone 8 mg PO ± one of the following:  Usually begins 6 to 7 hours after drug . Metoclopramide 0.5 to 2 mg/kg PO administration. every 4 to 6 hours  May persist for up to 120 hours. . Prochlorperazine 10 mg PO every 4 to • Some clinicians divide the daily antiemetic dose into 6 hours 2 doses on days when carboplatin is administered. . Promethazine 25 to 50 mg PO every 4 Cisplatin to 6 hours • Doses > 50 mg/m2 (single dose or cumulative over o Aprepitant 80 mg PO and dexamethasone consecutive days) causes delayed: 8 mg PO ± diphenhydramine 25 to 50 mg  Nausea in 78% of patients. PO every 6 hours if needed  Emesis in 61% of patients.  Patients with significant nausea or vomiting  May begin as soon as 16 hours after while receiving one of these regimens administration. should receive an agent from a different  Peak severity occurs at 48 to 72 hours after pharmacologic category.1-4 administration. Breakthrough Nausea and Vomiting1-4  Usually abates between 96 to 168 hours after administration.14 • Patients should have an antiemetic for breakthrough nausea. Cyclophosphamide • Recommended regimens: • Emesis is often delayed for up to 12 hours after  Metoclopramide 0.5 to 2 mg/kg PO every 4 to drug administration and may persist for up to 120 6 hours if needed, ± diphenhydramine 25 to 50 hours.12,15 mg PO every 6 hours if needed • Divide the daily antiemetic dose into 2 doses on  Prochlorperazine 10 mg PO every 4 to 6 hours days when cyclophosphamide is administered. Appendix B 521

HYDRATION  Usually:  Self-limiting Carboplatin  Resolves at the end of the infusion • If doses are adjusted for renal function (as in AUC  Additional doses of the drug can be dosing), no prophylactic hydration or diuretic use is administered without concern. required.16 Bleomycin19 Cisplatin • Can induce acute hypersensitivity reactions. • Can cause irreversible kidney damage by acute  Fever ± chills (common) tubular necrosis.  Most common in lymphoma patients • Maintain a urine output ≥ 75 to 100 mL/h for Pretreat with several hours before and after each dose. •  Acetaminophen • Numerous hydration and diuretic regimens have  Diphenhydramine been reported.  30 minutes prior to each dose of bleomycin • Except possibly the first treatment cycle, diuretics Test doses20 have no benefit over vigorous hydration.16 •  Generally not predictive. • One suggested regimen is D5W-NS or NS at 250  Not recommended. mL/h for 2 to 4 hours before and after each dose. • Oral hydration regimens are also used, but Docetaxel21,22 increased chloride from IV solutions may offer • Less likely to cause hypersensitivity reactions than better renal protection.16 paclitaxel • Mechanism of action of diuretics • Manufacturer recommends the following:  Intuitively supports their use to prevent  Dexamethasone 8 mg PO twice daily for 3 days nephrotoxicity.  Begin the day before the docetaxel infusion

 There is no evidence to recommend diuretics • Some clinicians add a histamine H2 antagonist ± a 17 over vigorous hydration. histamine H1 antagonist  If used, the following regimen is suggested: Cyclophosphamide  Cimetidine 300 mg or ranitidine 50 mg • Risk of hemorrhagic cystitis increases with18  Diphenhydramine 50 mg  Higher total doses.  All given IV over 30 minutes prior to  Radiation therapy. docetaxel • Patients should empty their bladder frequently. • Hydration reduces the risk of cystitis. Doxorubicin, Liposome Encapsulated23-26 • Encourage liberal fluid consumption (3 to 4 L/day) • Infusion-related reactions, particularly with the first  On treatment day(s). cycle of treatment  At least 24 hours after the last  Recommended prophylactic medications prior cyclophosphamide dose. to the first dose, and if necessary, prior to • Cystitis has been reported following a single IV subsequent doses: dose.18  Hydrocortisone 100 mg IV or dexamethasone 20 mg IV HYPERSENSITIVITY PRECAUTIONS  Diphenhydramine 25 mg or 50 mg IV  Cimetidine 300 mg or famotidine 20 mg IV Anthracyclines19  Given 30 minutes prior to liposomal • Daunorubicin/doxorubicin/epirubicin/idarubicin19 doxorubicin • Can cause acute hypersensitivity reactions • Very rare Oxaliplatin27-30 • No specific precautions • Reactions occur in 5% to 25% of patients. • “Flare reaction” • Moderate to severe reactions occur in < 1% to 9%  Not a true hypersensitivity reaction of patients.  Includes: • Most reactions occur at or after the seventh to ninth  Erythema treatment.  Pruritis • Lengthening the infusion time to 6 hours may  Urticaria reduce the incidence of hypersensitivity reactions.  Surrounds the injection site • Symptoms include the following:  Extends along the vein being infused  Common