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Home , Fosaprepitant, Maropitant, Netupitant, Rolapitant

Responding to the Challenge of -Induced Nausea and

Rudolph M. Navari, MD, PhD, FACP Professor of Medicine Associate Dean and Director Clinical Director, Harper Cancer Research Institute Indiana University School of Medicine – South Bend South Bend, Indiana

A nervous-appearing 68-year-old female presents to the infusion center to receive her 1st cycle of AC → T for newly diagnosed breast cancer. Her past medical history includes hypertension, hypothyroidism, and generalized anxiety. Her risk factors for chemotherapy-induced nausea and vomiting include all of the following EXCEPT …

25% 1. Female Gender 25% 2. Anxiety 25% 3. Highly emetogenic chemotherapy 25% 4. Advanced Age

1 Highly Emetogenic Chemotherapy

• Pre-chemotherapy (Prevent Acute N/V):

5-HT3 Receptor Antagonist NK-1 Receptor Antagonist • Post-chemotherapy (Prevent Delayed N/V): Dexamethasone NK-1 Receptor Antagonist

A 70-year-old male with a PMH of a-fib, MI, CAD, chronic alcoholism, and GERD presents for cycle #1 of carboplatin + paclitaxel → bevacizumab for advanced lung cancer. His risk factors for CINV include …

25% 1. History of chronic alcoholism 25% 2. Age 25% 3. Male gender 25% 4. History of GERD

2 Moderately Emetogenic Chemotherapy • Pre-chemotherapy (Prevent Acute N/V): Dexamethasone

5-HT3 Receptor Antagonist

• Post-chemotherapy (Prevent Delayed N/V): Dexamethasone

3 Patient Perceptions of the Most Severe Side Effects of Cancer Chemotherapy

Rank 19831 19932 19953 19994 1 Vomiting Nausea Nausea Nausea 2 Nausea Constantly Loss of hair Loss of hair tired 3 Loss of hair Loss of hair Vomiting Constantly tired 4 Thought of Effect on Constantly Vomiting coming for family tired treatment 5 Length of Vomiting Having to Changes in time have the way treatment an injection things taste takes

1. Coates A, et al. Eur J Cancer Clin Oncol. 1983;19:203-208; 2. Griffin AM, et al. Ann Oncol. 1996;7:189-195; 3. De Boer-Dennert M, et al. Br J Cancer. 1997;76:1055-1061; 4. Lindley C, et al. Cancer Pract. 1999;7:59-65.

Syndromes Associated With CINV (1 of 2)

• Acute emesis – Usually starts within 1-2 hours after administration – Peak intensity within 5-6 hours, resolution 12-24 hours • Delayed Emesis – Peak onset 48-72 hours after chemotherapy, diminishing after 1-3 day – Occurs in 50-90% of patients treated with highly emetogenic regimens – 35-70% with moderately emetogenic therapy – More common with platinum containing regimens • Breakthrough CINV – Nausea and vomiting occurring despite preventive therapy

4 Syndromes Associated With CINV (2 of 2)

• Anticipatory emesis – Associated with uncontrolled emesis during prior chemotherapy • Refractory CINV – N/V occurring during subsequent cycles of chemotherapy when prophylaxis or rescue therapy has failed in previous cycles • Potential to cause: – Dehydration and electrolyte imbalance – Impaired health-related quality of life • Negative impact on activities of daily living – Rehospitalization

Chemotherapy-Induced Emesis Risk Factors

• Patient-related risk factors1 – Younger age – Female gender – No/minimal prior history of alcohol use – Prior CINV –Anxiety • Treatment-related risk factors1,2 – Moderate to high emetogenicity of chemotherapy agents or regimens – Moderate to high drug dose

1. Gregory RE, et al. Drugs. 1998;55:173-189; 2. Hesketh PJ, et al. J Clin Oncol. 1997;15:103-109.

5 Risk Factors for CINV Chemotherapy-Specific Factors

• Use of moderately or highly emetogenic regimens such as – AC (Anthracycline + cyclophosphamide) - High – Carboplatin-based regimens - Moderate – -based regimens - High – Cyclophosphamide-based regimens - Moderate – FOLFOX/FOLFIRI - Moderate – ABVD - Moderate • Short IV infusion time • Repeated cycles of chemotherapy

Navari RM. J Support Oncol. 2003;1(2):89-103; Hesketh PJ, Oncologist. 1999;4(6):191-196; NCCN Clinical Practice Guidelines In Oncology. Antiemesis. Version 2.2010. Available at: http:://www.nccn.org.

6 Neurotransmitters in CINV

Dopamine/ DA RAs

Serotonin Endorphins

Emetic reflex

Substance P Acetylcholine

GABA Histamine

GABA = gamma-aminobutyric acid

Classes of Drug Pathway Target Side Effects Serotonin Acute Headache, constipation, asthenia, , sedation. , Delayed Prolonged INR, , slows dex, benzo metabolism Dexamethasone Prostaglandins? Delayed HTN, glucose, psych. Breakthrough Dopamine Breakthrough Akathisias, sedation, dizziness Gut motility, Delayed dopamine Dopamine Delayed Akathisias, dystonia, prolong QT, Breakthrough urinary retention, dizziness. Olanzapine Dopamine Acute, Sedation Serotonin Delayed Breakthrough Sedation, dizziness, dysphoria, Refractory euphoria, hallucinations Histamine Breakthrough Sedation

7 Dexamethasone

• Mechanism of action unknown • More effective than placebo and prochlorperazine in some controlled trials • Effective against vomiting caused by variety of anticancer agents, including cisplatin •  efficacy in combination antiemetic regimens • No significant side effects when used at recommended doses and schedules • Possible insomnia and hyperglycemia • No  incidence of infections or change in frequency and site of metastases • Inexpensive

The Best Dose of Dexamethasone?

• Rx: Dexamethasone • Indication: Acute emesis • Patients: Cisplatin • Results: All received ondansetron 8 mg IV randomized to single IV dexamethasone doses Dexamethasone N No Emesis No Nausea 4 mg 133 69% 61% 8 mg 136 69% 61% 12 mg 130 79% 67% 20 mg 131 83% 71% • Conclusions: No difference in adverse effects. Dexamethasone 20 mg should be the standard (20 vs 12 mg: 4% observed – 95% CI 5-14%)

The Italian Group. J Clin Oncol. 2000;18(19):3409-3422.

8 Mechanism of Action of Pharmacologic Therapies • Older agents of low therapeutic index – Dopamine RA’s • Dopamine receptor blockage in – Cannabinoids • antiemetic effect on enterochromaffin cells

•5HT3 RAs – Binding to 5HT3 receptors in periphery & CNS • Primary mechanism for acute emesis control • NK-1 RA’s – Predominantly central action • agents must cross blood-brain barrier

Hesketh PJ, et al. N Engl J Med. 2008;358:2482-2494

5-HT3 Receptor Antagonists

• First Generation: Ondansetron • Second Generation: Palonosetron

9 1st Generation 5-HT3 Antagonists Are Therapeutically Equivalent

• Highest Level Evidence & Pts receiving MEC* (N = 1085) Not Debated Oral granisetron 2 mg – MASCC 2004 IV ondansetron 32 mg – NCCN 2004 71.0 72.0 60.0 • 1st Generation Agents are 59.0 58.0 58.0 Therapeutically Equivalent – Dolasetron – Ondansetron

– Granisetron Complete Control (%) • 1st Generation oral and IV Total Nausea Emesis doses equally effective 80% of pts received prophylactic steroids *Cyclophosphamide 500-1200 mg/m2, carboplatin ≥ 300 mg/m2

MEC = moderately emetogenic chemotherapy.

Perez EA, et al. J Clin Oncol. 1998;16:754-760.

Mechanisms for Differences in

Efficacy of 5-HT3 antagonists

• Palonosetron has greater efficacy in prevention of acute & delayed CINV •Why?

– Higher binding affinity & longer t1/2 cannot fully account for this – Palonosetron has a unique binding site on the

5-HT3 receptor • Increases its affinity at other sites

Jin Y et al. Eur J Cancer Care (Engl). 2012 Apr 22. Epub ahead of print.

10 Palonosetron Indication

• Palonosetron 0.25 mg is indicated for: – The prevention of acute N/V associated with initial and repeat courses of moderately and highly emetogenic cancer chemotherapy – The prevention of delayed N/V associated with initial and repeat courses of moderately emetogenic cancer chemotherapy • The first and only 5-HT3 receptor antagonist specifically indicated for delayed CINV

Pooled Efficacy: Moderately Emetogenic Chemotherapy (N = 1132)

100.0

80.0 72.0 65.3 64.0 60.6 60.6 Palonosetron 0.25 mg 60.0 * * 46.8 **** Palonosetron 0.75 mg 40.0 Comparators (OND/DOL) 20.0 Complete response (%) 0.0 0-24 h 24-120 h *P ≤ 0.025

. Rubenstein EB, et al. Proc Am Soc Clin Oncol. 2003;22:729. Abstract 2932

11 Complete Response: Acute and Delayed Emesis With Highly Emetogenic Chemotherapy

Palonosetron 0.25 mg (n = 223) Palonosetron 0.75 mg (n = 223) 100 Ondansetron 32 mg (n = 221)

80 65.5 59.2 57.0

60 45.3 48.0 42.2 38.9 40.8 33.0 40

(% of patients) of (% 20 Complete Response 0 Acute: 0-24 Delayed: 24-120 Overall: 0-120 (Day 1) (Days 2-5) (Days 1-5)

Complete Response (CR) = no emesis, no rescue . Time (h)

Aapro M, et al. Support Care Cancer. 2003; Abstract A-17.

Complete Response in Patients Taking Concomitant Dexamethasone (N = 447)

100 Palonosetron 0.25 mg (n = 150) Palonosetron 0.75 mg (n = 150) 80 Ondansetron 32 mg (n = 147) 64.7 62.7 60 55.8 * * 42.0 41.3 40.7 35.3 40 28.6 25.2 (% of patients) of (%

Complete Response 20

0 Acute: 0-24 Delayed: 24-120 Overall: 0-120 (Day 1) (Days 2-5) (Days 1-5) Time (h) *97.5% CIs and 2-sided Fisher’s exact test (significance level = 0.025) indicate a difference between palonosetron and ondansetron. Of note, prophylactic dexamethasone was given at the investigator’s discretion (not randomized). Therefore, it is not appropriate to compare this subgroup to the overall population. Aapro M, et al. Support Care Cancer. 2003; Abstract A-17.

12 Palonosetron plus dexamethasone versus granisetron plus dexamethasone in patients receiving AC/EC and CDDP regimens

Saito M, Aogi K, Sekine I, et al. Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomized, comparative phase III trial. Lancet Oncol. 2009;10(2):115-124.

Palonosetron + Dexamethasone vs Granisetron + Dexamethasone in Japanese Patients Complete Response

90

80 † Palonosetron 0.75 mg IV (n = 555) 75.3 73.3 Granisetron 40 mcg/kg IV (n = 559) 70

60 56.8* 51.5* 50 44.5 40.4 40

30 (% of patients) 20 Complete Response 10

0 Acute (0-24 h) Delayed (24-120 h) Overall (0-120 h) * P = 0.0001 * P = 0.0001

†Statistical non-inferiority (lower limit of 95% CI > -10%; 95% CI [-2.7; 7.27]). *Statistically significant difference, significance level = 0.05). Saito M, et al. Lancet Oncol. 2009;10:115-124.

13 NK-1 Antagonists

• Aprepitant (PO)/ (IV) only commercially available agents • In active development – Netupitant, Rolapitant, • Prevents binding of substance P (SP) to NK-1 receptors • SP/NK1 RA complex is primarily associated with delayed emesis

Higa GM, et al. J Oncol Pharm Pract. 2006;12:201-209.; Munoz M, Covenas R. Discov Med. 101; 10:305-313.

Aprepitant Indications and Usage

• In combination with other antiemetic agents for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly and moderately emetogenic cancer chemotherapy, including high-dose cisplatin

14 Study Design Highly Emetogenic Chemotherapy

All patient received a chemotherapy regimen that included cisplatin > 50 mg (mean cisplatin dose = 80 mg/m2)

Aprepitant regimen Active-control regimen N = 550 N = 555

• Randomized, parallel, multicenter, double-blind controlled trial

Phase III Studies – Cycle I

Hesketh PJ, et al. J Clin Oncol. 2003;21(22):4112-4119; Poli-Bigelli S, et al. Cancer. 2003;97(12):3090-3098.

15 Warr DG, et al. J Clin Oncol. 2005 23(12):2822-2830.

Aprepitant in Moderately Emetogenic Chemotherapy: Complete Response (N = 857)

Aprepitant (n = 433) 100 Standard (n = 424)

76* 80 69 55 * 60 49 51 42 40 (% of patients) of (% 20 Complete Response (CR) 0 Acute: 0-24 Delayed: 24-120 Overall: 0-120 (Day 1) (Days 2-5) (Days 1-5) Time (h) *P < 0.05 Complete response (CR): no emesis and no rescue medication.

Warr DG, et al. J Clin Oncol. 2005;23:2822-2830.

16 Aprepitant in Moderately Emetogenic Chemotherapy: Percent of Patients With No Nausea Aprepitant (n = 430) 100 Standard (n = 424)

80 61 59 60

37 40 36 33 33 Nausea-Free (% of patients) of (% 20

0 Acute: 0-24 Delayed: 24-120 Overall: 0-120 (Day 1) (Days 2-5) (Days 1-5) Time (h)

No nausea: score < 5 mm on 0-100 mm VAS.

Warr DG, et al. J Clin Oncol 2005;23:2822-2830; Warr DG, et al. Support Care Cancer. 2004; Abstract A027.

Single-Dose Fosaprepitant for the Prevention of CINV

Grunberg, S et al. Single-dose fosaprepitant for the prevention of chemotherapy induced nausea and vomiting associated with cisplatin therapy. Randomized double-blind study protocol. EASE. J Clin Oncol. 2011;29:1495-1501

17 Complete Response and Vomiting Outcomes by Phase

Complete Response No Vomiting

100 100 89.0 88 89.4 89 90 90 80 74.6 75.676.4 71.972.3 74.3 74.2 80 72.9 70 70 60 60 50 50 40 40

Patients (%) Patients 30

Patients (%) Patients 30 20 20 10 10 0 0 Overall Phase Acute Phase Delayed Overall Acute Phase Delayed Phase Phase Phase

Fosaprepitant Aprepitant Fosaprepitant Aprepitant

Grunberg S, et al. J Clin Oncol. 2011;29:1495-1501.

Netupitant: An Oral Fixed-Dose Combination of Netupitant and Palonosetron

Netupitant Aprepitant

• Selective neurokinin type 1 receptor antagonist (NK1 RA) • Competitively binds to and blocks activity of substance P receptors • High binding affinity, long half-life (90 hr) vs 9-13 hrs with aprepitant • High (> 90%), long-lasting (> 96 hr) brain receptor saturation after single oral dose • Metabolized by CYP3A4 • Moderate inhibitor of CYP3A4

National Cancer Institute Drug Dictionary. Available at: http://www.cancer.gov/drugdictionary?cdrid=699733. Accessed May 4, 2013; Data on file. Eisai Inc; Woodcliff Lake, NJ. Aprepitant prescribing information, 2008.

18 NEPA, A Fixed-Dose Combination of Netupitant and Palonosetron vs Palonosetron Alone for the Prevention of CINV Following MEC

Presented at the American Society of Clinical Oncology 2013 Annual Meeting Aapro M, Rossi G, Rizzi G, et al. J Clin Oncol. 2013;31(suppl). Abstract LBA 9514.

NEPA vs Palonosetron in MEC Primary Endpoint: Complete Response Rates

NEPA + DEX Palonosetron + DEX 90 88 85

80 77 74 70 70 67

60

50

40

30 (% of patients) 20 Complete Response 10

0 Acute (0-24 h) Delayed (25-120 h) Overall (0-120 h) *P = 0.047 *P = 0.0001 *P = 0.0001

*Statistically significant difference, significance level = 0.05.

Aapro M, et al. J Clin Oncol. 2013;31(suppl). Abstract LBA 9514.

19 NEPA, A Novel Combination of Netupitant and Palonosetron for the Prevention of CINV Following HEC

Presented at the American Society of Clinical Oncology 2013 Annual Meeting Hesketh P, Rossi G, Rizzi G, et al. J Clin Oncol. 2013;31(suppl). Abstract 9512.

NEPA for CINV Prevention in HEC Regimens Primary Endpoint: Complete Response Rates

P = 0.018 P = 0.017 P = 0.004 P = 0.027

PALO NEPA 100 NEPA 200 NEPA 300 Acute N/V 89.7% 93.3% 92.7% 98.5% (Hrs 0-24) P = 0.007 Delayed N/V 80.1% 90.4% 91.2% 90.4% (Hrs 25-120) P = 0.018 P = 0.010 P = 0.018

Hesketh P, et al. J Clin Oncol. 2013;31(suppl). Abstract 9512.

20 Olanzapine and palonosetron for the prevention of chemotherapy-induced nausea and vomiting Navari RM, et al. Supportive Care Cancer. 2007;15(11):1285-1291.

Palonosetron + Dexamethasone + Olanzapine Study Design • Multicentre, phase II, open-label study • Chemotherapy-naïve patients receiving moderately (MEC) or highly emetogenic chemotherapy (HEC) • Schema

Day 1 Day 2 Day 3 Day 4 Palonosetron 0.25 mg IV - - - 20 mg (HEC) Dexamethasone or --- 8 mg (MEC) Olanzapine 10 mg PO 10 mg PO 10 mg PO 10 mg PO

• Endpoints: Complete response (no emesis, no rescue), no Nausea (score = 0, MD Anderson Symptom Inventory 0-10 scale)

Navari RM, et al. Supportive Care Cancer. 2007;15(11):1285-1291.

21 Palonosetron + Dexamethasone + Olanzapine Nausea Assessment

No Nausea in HEC (n = 8) 100 100 No Nausea in MEC (n = 32) 100 78 78 80

60 50 50

40

20

0 Acute (0-24 h) Delayed (24-120 h) Overall (0-120 h)

• Chemotherapy-naïve; 55% female; median age 60 years (range 38-84)

Navari RM, et al. Supportive Care Cancer 2007;15(11):1285-1291.

Olanzapine + + Dex Vs Azasetron + Dex • Multicentre, phase III, open-label study • 229 patients receiving moderately (MEC) or highly emetogenic chemotherapy (HEC) • Schema Day 1 Day 2 Day 3 Day 4 Oln + Aza + Olanzapine Dex Oln Oln Oln

---

Azasetron Aza + Dex Dex Dex Dex • Endpoints: Complete response (no emesis, no rescue)

. Tan L, et al. J Exp Clin Cancer Res. 2009;28:131-138

22 AZA+OLN vs. AZA Complete Response Highly Emetogenic Chemotherapy

91 89

78.5 78.5

56.5 56.5 th Complete Responseth Complete

Complete Response AZA+OLN Complete Response AZA Percent of Patients wi

Acute (0-24 h) Delayed (24-120 h) Overall (0-120 h)

Efficacy Outcome Highly Emetogenic Chemotherapy

100 95 No Nausea HEC

90 87

80

70 70 70

60 Oln+Aza Aza Patients 50 of

40 Percent 30 30 28

20

10

0 Acute Delayed Overall

. Tan L, et al. J Exp Clin Cancer Res. 2009;28:131-138

23 AZA+OLN vs. AZA Complete Response Moderately Emetogenic Chemotherapy

97 97 89 89

76 76 th Complete Responseth Complete

Complete Response AZA+OLN Complete Response AZA Percent of Patients wi

Acute (0-24 h) Delayed (24-120 h) Overall (0-120 h)

Efficacy Outcome Moderately Emetogenic Chemotherapy

120 No Nausea MEC

100 98 94

83 83 80

Patients 60 58 Oln + Aza

of 56

Aza Percent 40

20

0 Acute Delayed Overall

. Tan L, et al. J Exp Clin Cancer Res. 2009;28:131-138

24 Olanzapine versus aprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV): A randomized Phase III trial

R. M. Navari, S. E. Gray and A. C. Kerr

J Supp Oncol 9:188-195, 2011

Olanzapine versus Aprepitant in HEC patients

• A phase III trial was performed for the prevention of CINV in chemotherapy-naïve patients receiving HEC (cisplatin, 70 mg/m2 or doxorubicin, 50 mg/m2) comparing OLN to APR in combination with palonosetron (PALO) and dexamethasone (DEX) • The OLN regimen was 10 mg of PO OLN, 0.25 mg of IV PALO, and DEX 20 mg IV on the day of chemotherapy, Day 1, and 10 mg/day of PO OLN alone on Days 2-4 after chemotherapy • The APR regimen was 125 mg of PO APR, 0.25 mg IV PALO, and 12 mg IV DEX, Day 1, and 80 mg PO APR, 4 mg DEX BID, Days 2-4 • 251 patients (median age 62 years, range 39-81; 164 females; ECOG PS 0,1) consented to the protocol and 241 were evaluable Navari RM et al. J Support Oncol 9:188-195, 2011

25 Complete Response

OLN + PAL + DEX vs APR + PAL + DEX Complete Response

97 Complete Response OPD (n=121)

87 Complete Response APD (n=120)

77 77 73 73 Percent of Patients with Complete Response Complete with Patients of Percent

Acute (0-24 h) Delayed (24-120 h) Overall (0-120 h)

Navari R, et al. J Suppl Onc. In Press.

No Nausea

OLN + PAL + DEX vs APR + PAL + DEX 87 87 No Nausea No Nausea OPD (n=121)

No Nausea APD (n=120)

69 69

38 38 Percent No Nausea withof Patients Percent

Acute (0-24 h) Delayed (24-120 h) Overall (0-120 h)

Navari R, et al. J Suppl Onc. In Press.

26 Results / Conclusion • OLN group: – CR (no emesis no rescue) was 97% for the acute period (24 h post- chemotherapy) – 77% for the delayed period (days 2-5 post-chemotherapy) – 77% for the overall period (0-120 h) for 121 patients receiving the OLN regimen

• APR group: – CR was 87% for the acute period – 73% for the delayed period – 73% for the overall period in 120 patients receiving the APR regimen

• Patients without nausea was: OLN: 87%, acute; 69%, delayed; 69%, overall; APR: 87%, acute; 38%, delayed; and 38% overall. There were no grade 3 or 4 toxicities

• OLN was comparable to APR in the control of CINV in patients receiving HEC. Nausea was better controlled with OLN

Navari R, et al. J Suppl Onc. In Press.

A nervous-appearing 68-year-old female presents to the infusion center to receive her 1st cycle of AC → T for newly diagnosed breast cancer. Her past medical history includes hypertension, hypothyroidism, and generalized anxiety.

The preferred antiemetics are:

Pre-chemotherapy: (1) Dexamethasone (2) Palonosetron (3) Arepitant po or Fosaprepitant IV Post chemotherapy: (1) Dexamethasone , Days 2-4 (3) Aprepitant, Days 2,3 (Omit if Fosaprepitant used on Day 1)

NOTE: No 5-HT3 receptor antagonists post chemotherapy

27 A 70-year-old male with a PMH of a-fib, MI, CAD, and GERD presents for cycle #1 of carboplatin + paclitaxel → bevacizumab for advanced lung cancer.

The preferred antiemetics are:

Prechemotherapy: (1) Dexamethasone (2) Palonosetron Post chemotherapy: (1) Dexamethasone , Days 2-4

NOTE: No 5-HT3 receptor antagonists post chemotherapy

Antiemetic Guidelines: High Emetic Risk Emetogenic Risk NCCN* ASCO Category

Acute (day 1): 5-HT3 antagonist plus corticosteroid High plus NK1 antagonist (NCCN lists palonosetron as preferred)

Delayed (days 2-4): Corticosteroid plus NK1 antagonist

Acute and Delayed: As Acute: As above AC Regimens above Delayed: NK1 antagonist * +/- 0.5 – 2mg PO or IV every 4-6 h +/- H2 blocker or proton pump inhibitor

NCCN Clinical Practice Guidelines in Oncology. Antiemesis. V.1.2012. Available at: http://www.nccn.org/professionals/physician_gls/PDF/antiemesis.pdf ; Kris et al.. J Clin Oncology. 2011; 29:4189-4198.

28 Antiemetic Guidelines: Moderate Emetic Risk Emetogenic NCCN* ASCO Risk Category

Moderate Acute (day 1): 5-HT3 Acute (day 1): : antagonist plus Palonestron plus corticosteroid (palonosetron corticosteroid preferred) Delayed (days 2-3): Optional: NK1 antagonist Corticosteroid Delayed (days 2-3): Corticosteroid

* +/- Lorazepam 0.5 – 2mg PO or IV every 4-6 h +/- H2 blocker or proton pump inhibitor

NCCN Clinical Practice Guidelines in Oncology. Antiemesis. V.1.2012. Available at: http://www.nccn.org/professionals/physician_gls/PDF/antiemesis.pdf ; Kris et al. J Clin Oncology, 2011; 29:4189-4198.

ANTIEMETIC GUIDELINES

ASCO: WWW.PLWC.ORG NCCN: WWW.NCCN.ORG MASCC: WWW.MASCC.ORG

29 Key Points

• Treatment of the nausea associated with emetogenic chemotherapy is still a problem. Olanzapine appears to be an effective agent. • Prevention is the goal of management • The development of serotonin antagonists and the neurokinin-1 antagonist, aprepitant, have resulted in a significant improvement in the treatment of CINV • Corticosteroids are useful antiemetics, they provide synergy with 5-HT3 antagonists and play an important role in the treatment of delayed emesis • Prescribe drug combinations for the entire time of risk • Research must continue until all nausea and vomiting associated with cancer are prevented. The goal of therapy is NO N / V for at least 5 days following chemotherapy • Guidelines have been established to help manage populations of patients however outliers do exist

30