1. University of Auckland Nursing 785 Assignment 3. Marc McLaughlin 5289608

2. Overview Pharmacotherapuetic management of chemotherapy induced nausea and vomiting (CINV). Review of the antiemetic regime for a patient receiving antineoplastic chemotherapy with a high emetogenic profile.

3. Patient History 51 year old female. Breast cancer detected by routine screening mammogram and subsequent core biopsy. Stage IIA (T1b N1a MX. ER 3+, PR negative, HER 2 negative) Wide local excision and axillary clearance: 1/20 lymph nodes. Adjuvant chemotherapy: AC/Paclitaxel (Doxorubicin 60mg/m 2 Cyclophosphamide 600mg/m2. Paclitaxel 80mg/m2) + Hormone therapy. Risk of recurrence estimated to be 40% with surgery alone. With combined treatment reduced to 15%. (Adjuvant Online Database)

4. Implications of suboptimal antiemetic control Decreased quality of life. Compromised patient compliance. Physical deterioration and acute admissions. Treatment delays or potentially abandonment. Deviation from optimal treatment regime and dose intensity. Navari, RM. (2009) Pharmacological Management of Chemotherapy-Induced Nausea and Vomiting. Drugs. 69;(5). 515-533. Cohen et al. (2007) Chemotherapy-induced nausea and vomiting: incidence and impact on patient quality of life at community oncology settings. Support Cancer Care. 15;(5). 497-503.

5. Risk Factors – Chemotherapy Regime Highly Emetogenic : 90% incidence of emesis Moderately Emetogenic: 30%-90% incidence of emesis Lowly Emetogenic: 10%-30% incidence of emesis Minimally Emetogenic: <10% incidence of emesis Hawkins, R & Grunberg, S. (2009) Chemotherapy-induced nausea and vomiting: Challenges and Opportunities for Improved Patient Outcomes. Clinical Journal of Oncology Nursing. 13;(1). 54-64.

6. Risk Factors – Chemotherapy Regime As single agent treatments, Doxorubicin and Cyclophosphamide classified as ‘moderately’ emetogenic. Navari, RM. (2009) Pharmacological Management of Chemotherapy-Induced Nausea and Vomiting. Drugs. 69;(5). 515-533. However, when combined as ‘AC’ regime classification increases to ‘highly’ emetogenic. (90% emesis incidence) Basch, E et al. (2011) Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. Journal of Clinical Oncology. 29:(31). 4189-4198.

7. Risk Factors – Patient Age < 50 years. Female. Minimal alcohol history/intake. History of motion sickness and/or morning sickness during pregnancy. History of previous chemotherapy induced nausea and vomiting. Vidal, C. (2011) Chemotherapy induced nausea and vomiting: a European perspective. British Journal of Nursing. 20:(10). 22-28. Navari, RM. (2009) Pharmacological Management of Chemotherapy-Induced Nausea and Vomiting. Drugs. 69;(5). 515-533. Hawkins, R & Grunberg, S. (2009) Chemotherapy-induced nausea and vomiting: Challenges and Opportunities for Improved Patient Outcomes. Clinical Journal of Oncology Nursing. 13;(1). 54-64.

8. Recommendations ASCO: Three drug combination recommended in the ‘highly’ emetogenic setting. Substance P neurokinin 1 (NK 1) receptor antagonist (d1-3) 5-HT 3 receptor antagonist (d1) Dexamethasone (d1-3) Basch, E et al. (2011) Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. Journal of Clinical Oncology. 29:(31). 4189-4198.

9. Antiemetic regime Aprepitant 125 mg po d1; 80 mg po d2+3. NK 1 receptor antagonist Ondansetron 8 mg po b/d d1-3. 5-HT 3 receptor antagonist Dexamethasone 12mg po d1; 8mg po d2+3. Synthetic corticosteroid

10. Pharmacotherapuetic monitoring Efficacy of the combined aprepitant, ondansetron and dexamethasone regime in the control of acute and delayed nausea and/or emesis. Potential risk of drug interaction between Aprepitant and Dexamethasone.

11. Efficacy Patient has presently undergone two cycles of AC out of a total of four planned cycles. Cycle 1: grade 2 nausea. No emesis. Cycle 2: grade 1 nausea. No emesis. No requirement of acute antiemetic rescue. No mandate to deviate from optimal treatment plan.

12. Risk of drug interaction Aprepitant inhibits CYP3A4 system Metabolism of dexamethasone (CYP3A4 substrate) subsequently inhibited. Potential for elevated plasma concentration of dexamethasone. (oral dose requires approx 50% reduction) McCrea et al. (2003). Effects of the neurokinin 1 receptor antagonist aprepitant on the pharmacokinetics of dexamethasone and methylprednisolone. Clin Pharm Ther.74: 17-24 Nakade et al. (2008). Population pharmacokinetics of aprepitant and dexamethasone in the prevention of chemotherapy- induced nausea and vomiting. Cancer Chemother Pharmacol. 63: 75-83. Dando, TM & Perry,CM. (2004) Aprepitant: A review of its use in the prevention of chemotherapy-induced nausea and vomiting. Drugs. 64:(7). 777-794.

13. Monitoring Currently no dose-limiting toxicity evident or requirement for adjusting present antiemetic regime. Patient reports minor transient insomnia on days taking dexamethasone. Not significantly diverged from baseline sleeping pattern. No other adverse effects from corticosteroid administration. Present antiemetic regime demonstrating satisfactory efficacy and tolerability for patient.

14. Monitoring Continued close monitoring required for duration of treatment plan. Transition to more appropriate antiemetic regime when AC completed and commencing Paclitaxel component of treatment plan.

15. University of Auckland Nursing 785 Assignment 3. Marc McLaughlin 5289608