1. Held in conjunction with the Association for Value-Based Cancer Care’s (AVBCC’s) First Annual Stakeholder Integration Conference

3. Chemotherapy-Induced Nausea and Vomiting (CINV) Consequences of CINV: – Non-compliance with treatment – Treatment interruptions – Unwillingness or inability to eat and/or drink – Nutritional deficits – Decreased quality of life, survival? Treatment (dose, type of agent) Personal factors (age, history of CINV, ETOH use, concurrent radiation) Feyer, P., & Jordan, K. Update and new trends in antiemetic therapy: the continuing need for novel therapies. Annals of Oncology.

4. Characteristics of Delayed-Onset CINV Nausea and vomiting >24 hrs after chemo Up to 7 days following treatment More common if treated with high doses of chemotherapy Stomach upset up to 72 hours following chemo With or without preventative therapy NCCN Guidelines v3.2011. Available: http://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf. Accessed February 23, 2011.

5. Classification and Risk for CINV Risk of emesis Classification of CINV >90%High-risk or highly emetogenic chemotherapy (HEC) 30%–90%Moderate emetogenic chemotherapy (MEC) 10%–30%Low emetic risk <10% ofMinimally emetogenic NCCN Guidelines v3.2011. Available: http://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf. Accessed February 23, 2011.

6. Level 1 Level 2 Level 3 Level 4 (>10%) (10%–30%) (31%–90%) (>90%) BleomicinBortezomib Carboplatin Carmustine Busulfan CetuximabCyclophoshamide Cisplatin Vinbalstine Cytarabine (>1.5 g/m2) Cyclophosphamide Vinorelbine (>100 mg/m2) Cytarabine (>1.5 g/m2) Fludrabine Docetaxel Daunorubicin Dacarbazine Cladribine EtoposideDoxorubicin Mechlorethamine Bevacizumab Flouracil Epirubicin Streptozocin Gemcitabine Idarubicin IxabepiloneIfosfamide Lapatinib Irinotecan Methotrexate Oxaliplatin Mitomicyn Mitoxantrone Paclitaxel Pemetrexed Temsirolimus Topotecan Trastuzumab Minimally emetogenic Is Your Patient at Risk for CINV? Low risk Moderate High Risk From: Tuca, A. (2009). Use of granisetron transdermal system in the prevention of chemotherapy-induced nausea and vomiting: a review. Cancer Management and Research, Volume 2010:2 Pages 1 - 12 DOI 10.2147/CMR.S4953, NCCN guidelines v3.2011

7. Chemotherapy-Induced Nausea and Vomiting (CINV): Novel Agents Prophylaxis and treatment of CINV includes novel and traditional therapies: – 5-hydroxytryptamine 3 (5-Ht3) receptor antagonists – Neurokinin 1 ( NK1) receptor antagonists, dopamine receptor antagonists – Corticosteroids, benzodiazepines, neuroleptics and cannabinoids Feyer, P., & Jordan, K. Update and new trends in antiemetic therapy: the continuing need for novel therapies. Annals of Oncology ; NCCN Guidelines v3.2011. Available: http://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf. Accessed February 23, 2011.

8. Antiemetic Prevention is Based on Risk Category Delayed: Prophyllaxis 2-3 days after (ASCO); 2- 4 days (NCCN) ASCO, NCCN and MSACC: – All unanimously suggest a combination of a 5- HT 3 RA, dexamethasone, and aprepitant within 24 hours for acute CINV with highly emetogenic chemotherapy – Questions remain regarding best use of aprepitant, dexamethasone, lorazepam for delayed onset CINV in moderate or severely emetogenic regimens

9. Jordan, K. et al. Oncologist 2007;12:1143-1150

10. General Recommendations for CINV: Sequencing Low Emetic Risk Chemo Moderate Emetic Risk Chemo High Emetic Risk Chemo Dexamethasone (if appropriate) 2-drug regimen (5HT3 receptor antagonist + dexamethasone PLUS One of these agents for delayed CINV +/- Lorazepam, H2 blocker or PPI 3-drug regimen (5HT3 receptor antagonist, dexamethasone + aprepitant (acute emesis) AND 2-drug regimen combining aprepitant and dexamethasone for delayed emesis +/- Lorazepam, H2 blocker or PPI Kris MG, Hesketh PJ, Somerfield MR, et al. American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006.J Clin Oncol. 2006;24:2932–2947; NCCN Guidelines v3.2011. Available: http://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf. Accessed February 23, 2011.

11. Dose and Sequencing: Low-Risk Emetogenic Regimens ASCO: Dexamethasone (8 mg) if appropriate No routine preventive use of antiemetic for delayed emesis NCCN: Metoclopramide w/wo diphenhydramine; Dexamethasone (12 mg) or Prochlorperazine, w/wo lorazepam

12. Dose and Sequencing of Novel Agents: Moderately Emetogenic - D1 5HT3 agonist : – Dolasetron 100mg PO or – Granisetron 1 mg PO BID or 2 mg daily or – Ondansetron 16-24mg PO or up to 8-12mg IV or – Palonesetron 0.25mg IV day 1 only PLUS Dexamethasone 12mg PO/IV w/wo NK1 agonist: – Aprepitant 125mg PO (with dex) – Fosaprepitant 115mg IV – Casoprepitant Lorazepam.5mg-2mg PO/IV/SL q4-6h PRN H2 blocker, PPI Kris MG, Hesketh PJ, Somerfield MR, et al. American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006.J Clin Oncol. 2006;24:2932–2947; NCCN Guidelines v3.2011. Available: http://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf. Accessed February 23, 2011. Grunberg, S., Warr, D., Gralla, R., Rapoport, B., Hesketh, P., Jordan, K., et al. (2010). Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity—state of the art. Supportive Care in Cancer, 1-5.

13. Dose and Sequencing of Novel Agents: Moderately Emetogenic- Day 2-4 5HT3 agonist- Monotherapy – Dolasetron 100mg PO or – Granisetron 1 mg PO BID or 2 mg daily or – Ondansetron 8-16mg PO BID OR Dexamethasone monotherapy 8mg PO/IV – w/wo NK1 agonist (if used D1): – Aprepitant 80mg PO Lorazepam.5mg-2mg PO/IV/SL q4-6h PRN H2 blocker, PPI PRN breakthrough: – Olanzapine, cannabinoids, phenothiazine

14. Dose and Sequencing of Novel Agents: Highly Emetogenic-D1 5HT3 agonist : Dolasetron 100mg PO or Granisetron 1 mg PO BID or 2 mg daily or Ondansetron 16-24mg PO or up to 8-12mg IV or Palonesetron 0.25mg IV day 1 only – PLUS Dexamethasone 12mg PO/IV With NK1 agonist: – Aprepitant 125mg PO (with dex) – Fosaprepitant 150mg – Casoprepitant Lorazepam.5mg-2mg PO/IV/SL q4-6h PRN H2 blocker, PPI Kris MG, Hesketh PJ, Somerfield MR, et al. American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006.J Clin Oncol. 2006;24:2932–2947; NCCN Guidelines v3.2011. Available: http://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf. Accessed February 23, 2011. Grunberg, S., Warr, D., Gralla, R., Rapoport, B., Hesketh, P., Jordan, K., et al. (2010). Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity—state of the art. Supportive Care in Cancer, 1-5.

15. Dose and Sequencing of Novel Agents: Highly Emetogenic- Day 2-4 5HT3 agonist- Monotherapy Dolasetron 100mg PO or Granisetron 1 mg PO BID or 2 mg daily or Ondansetron 8-16mg PO BID OR Dexamethasone monotherapy 8mg PO/IV With NK1 agonist: – Aprepitant 80mg PO Lorazepam.5mg-2mg PO/IV/SL q4-6h PRN H2 blocker, PPI PRN breakthrough: – Olanzapine, cannabinoids, phenothiazine

16. Interactions/Considerations: Novel Agents Aprepitant – Metabolized by cytochrome P450 (CYP) 3A4 – AVOID pimozide, terfenadine, astemizole, or cisapride – Warfarin –Decreased INR – Decreased efficacy of hormonal contraceptives (up to 28 days after) – Dexamethasone should be decreased 50% when used in combination with aprepitant EMEND package insert. Accessed online February 23, 2011 at http://www.merck.com/product/usa/pi_circulars/e/emend_iv/emend_iv_pi.pdf

17. Considerations with Novel Agents Dexamethasone Highly effective for HEC – Underutilized antiemetic but affects nearly every body system Side effects (select) – moderate-to-severe insomnia (45%), – indigestion/epigastric discomfort – agitation – increased appetite – weight gain and acne Faiman, B., Bilotti, E., Mangan, P., & Rogers, K. (2008). Steroid-Associated Side Effects in Patients With Multiple Myeloma: Consensus Statement of the IMF Nurse Leadership Board. Clinical Journal of Oncology Nursing, 12(0), 53-62; NCCN guidelines

18. Side Effect Management of Novel Agents Most are well tolerated Less effective if not prescribed appropriately Risk –stratify patients – How emetogenic is the regimen? Previous CINV Patient variability/patient-related risk – Female sex, age, emesis during pregnancy, motion sickness, alcohol use, tumor burden – Other: anxiety, concomitant medications, oral chemotherapy/polypharmacy, concurrent medical conditions, hydration

19. Key Points Patients with cancer and who receive chemotherapy are at risk to develop CINV Each patient should be evaluated for personal risk Moderate to highly emetogenic chemotherapy requires prophyllactic antiemetics PLUS abortive therapy