SUPPORTIVE CARE NATIONAL COMPREHENSIVE CANCER NETWORK (NCCN) ANTIEMETIC GUIDELINE UPDATES, VERSION 3.2018 MEENAKSHI SHELAT, PHARMD, BCOP DARTMOUTH-HITCHCOCK MEDICAL CENTER NOVEMBER 2018
DISCLOSURES • I have nothing to disclose related to the content of this presentation 2
LEARNING OBJECTIVES • Explain the basic physiology of chemotherapy-induced nausea and vomiting • Review recent updates that highlight agents/dosages classified as highly emetogenic to ensure adequate guideline-based prophylaxis • Recognize agents that are categorized as medium, low, and minimal emetogenic risk to recommend appropriate therapy 3
ADDRESSING CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING (CINV) • Need to overcome challenges with implementing guideline-based updates to ensure optimal care for patients experiencing CINV - Education, training, communication, order-sets - Consider patient regimen and clinical, social, financial factors • Pharmacists play a critical role in education, communication, and counseling 4 Aapro M et al. Ann Oncol. 2012 Aug;23(8):1986-92. Barbour, Sally and Frame, David. Chemotherapy-induced Nausea and Vomiting: The Pharmacist’s Role in Integrating Clinical Guidelines into Patient Care. Presented as a Live Webinar . ASHP 2016.
PHYSIOLOGY MECHANISMS OF ACTION • Neurokinin 1 receptor antagonist (NK 1 RA) • 5-hydroxytryptamine receptor antagonist (5-HT 3 RA) 5 https:// www.researchgate.net/figure/Pathophysiology-of-chemotherapy-induced-nausea-and- vomiting_fig2_321927048 National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018
PHYSIOLOGY MECHANISMS OF ACTION • NK 1 receptor antagonist • 5-HT 3 receptor antagonist • Dopaminergic receptor antagonist • Cannabinoid 6 https://openi.nlm.nih.gov/detailedresult.php?img=PMC4034105_pharmaceuticals-03-02930-g001&req=4 National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018
TYPES OF EMESIS Chemotherapy-Induced (Intravenous, IV and Oral, PO) Anticipatory, Acute, Delayed, Breakthrough, Refractory Radiation-Induced Radiation therapy (RT) Upper abdomen/local sites, Total Body Irradiation (TBI), Chemotherapy and RT 7 National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018
PATIENT-FOCUSED GOAL: PREVENTING NAUSEA AND VOMITING Acute Delayed ≤ 24 hrs > 24 hrs Moderate High 8 National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018
PATIENT CASE AND DISCUSSION • Pt ND is a 62 year old female Stage IIIC1 grade 2 endometrial cancer, s/p robotically assisted total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, sentinel lymph node dissection • Past medical history: reports low alcohol intake • Plan to start paclitaxel 175 mg/m 2 and carboplatin AUC 5, followed by pelvic radiation therapy 50 Gy or 45 Gy with cisplatin for chemosensitization, with further chemotherapy to follow 9
CINV IS MULTIFACTORIAL • Emetogenic risk of agents in regimen (high, moderate, low, minimal) • Female • Younger age (less than 50 yrs) • History of low alcohol intake • History of motion sickness • History of emesis during pregnancy 10 Heskith P. Oncologist . 1999; 4:191-6. National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018 Barbour, Sally and Frame, David. Chemotherapy-induced Nausea and Vomiting: The Pharmacist’s Role in Integrating Clinical Guidelines into Patient Care. Presented as a Live Webinar . ASHP 2016. Aapro M et al. Ann Oncol. 2012 Aug;23(8):1986-92.
DRUG CLASSES NK 1 receptor Class 5‐HT 3 receptor antagonist antagonist Corticosteroids Thiobenzodiazepine Examples aprepitant ondansetron dexamethasone (dex) olanzapine (PO) ‐ injectable emulsion palonosetron (IV) ‐ oral (PO) granisetron fosaprepitant ‐ subcutaneous (SQ) ‐ intravenous (IV) ‐ intravenous netupitant (PO) ‐ transdermal dolasetron rolapitant (PO) oral netupitant/palonosetron (PO) fosnetupitant/palonosetron (IV) Monitoring/ CYP3A4 inhibitor Headache Insomnia CNS depression, sedation dex dose reduction Constipation Hyperglycemia Weight gain Common QTc/Cardiac Dyspepsia Orthostatic hypotension Note: rolapitant is not Side Effects QTc a CYP3A4 inhibitor or 11 Interaction‐ metoclopramide/ inducer haloperidol – EPS Roila, F. et a. Annals of Oncology , Volume 27, Issue suppl_5, 1 September 2016, Pages v119–v133 National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018
OTHER DRUG CLASSES/PATHWAYS Class Benzodiazepine Cannabinoid Phenothiazine Dopaminergic receptor antagonist Examples lorazepam dronabinol prochlorperazine metoclopramide* nabilone promethazine haloperidol** CNS depression CNS depression Increased risk of EPS Increased risk of EPS Monitoring/ Useful for anxiety May help appetite CNS depression QTc Common Sedation: Side Effects promethazine > *Diarrhea, but helps prochlorperazine gastroparesis *Tardive dyskinesia **CNS depression 12 National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018
RECENT CLINICAL TRIALS AND PAPERS Trial Efficacy Safety Benefit in delayed emesis Somnolence A double-blind randomized phase II dose-finding study 5 mg (CR 85.7%, P < 0.001) 5 mg: 45.5% of olanzapine 10 mg or 5 mg for the prophylaxis of 10 mg (CR 77.6%, P = 0.01) 10 mg: 53.3% emesis induced by highly emetogenic cisplatin-based chemotherapy. Yanai T et al, Int J Clin Oncol. 2018 Apr;23(2):382-388. Papers Gilmore, J et al, Recent advances in antiemetics: new formulations of 5HT 3 -receptor antagonists. Cancer Manag Res. 2018 Jul 3;10:1827-1857. Navari, R et al, Evolving role of neurokinin 1-receptor antagonists for chemotherapy-induced nausea and vomiting. Onco Targets Ther. 2018; 11: 6459–6478. 13
TYPES OF EMESIS Chemotherapy-Induced (Intravenous, IV and Oral, PO) Anticipatory, Acute, Delayed, Breakthrough, Refractory Radiation-Induced Radiation therapy (RT) Upper abdomen/local sites, Total Body Irradiation (TBI), Chemotherapy and RT 14 National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018
UPDATES REGARDING AGENTS AND REGIMENS Type of Emesis/ Agent Formulation Emetic Risk High cisplatin IV carboplatin ≥ 4 IV anthracycline/cyclophosphamide IV Transplant regimen such as CBV IV Moderate to High enasidenib PO midostaurin PO niraparib PO Moderate liposomal encapsulation cytarabine and daunorubicin IV Low olaratumab IV Minimal to Low abemaciclib PO brigatinib PO nertainib PO ribociclib PO Minimal avelumab IV 15 rituximab and hyaluronidase SQ National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018
REFER TO MOST UPDATED VERSION OF GUIDELINES: INCLUDING NATIONAL COMPREHENSIVE CANCER NETWORK (NCCN) Type of Emesis/ Day 1 Subsequent Days Emetic Risk Days 2,3,4 for high; Days 2,3 for moderate CINV – High NK 1 RA + 5-HT 3 RA + dex aprepitant PO if PO used Day 1 or *** dex olanzapine + palonosetron + dex olanzapine olanzapine + NK 1 RA + 5-HT 3 RA + dex aprepitant PO if PO used Day 1, olanzapine + dex CINV - Moderate 5-HT 3 RA + dex 5-HT 3 RA *** or dex *** May not be needed olanzapine + palonosetron + dex olanzapine 5-HT 3 RA + dex (± NK 1 RA) aprepitant PO if PO used Day 1 ± dex dex CINV - Low metoclopramide prochlorperazine 5-HT 3 RA CINV - Minimal No routine prophylaxis regimen granisetron PO daily or ondansetron PO BID ± dex RT – local granisetron PO daily or ondansetron PO BID/TID ± dex TBI See above Chemo and RT 16 Hesketh, PJ et al Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update Summary . National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018 Journal of Oncology Practice 2017 13:12, 825-830
REFER TO MOST UPDATED VERSION OF GUIDELINES: INCLUDING NATIONAL COMPREHENSIVE CANCER NETWORK (NCCN) Type of Day 1 Subsequent Days Emesis, Days 2,3,4 for high; Days 2,3 for moderate Emetic Risk *** May not be needed NK 1 RA + 5-HT 3 RA + dex aprepitant PO if PO used Day 1 or *** dex CINV olanzapine + palonosetron + dex olanzapine High olanzapine + NK 1 RA + 5-HT 3 RA + dex aprepitant PO if PO used Day 1, olanzapine + dex CINV 5-HT 3 RA + dex 5-HT 3 RA *** or dex olanzapine + palonosetron + dex olanzapine Moderate 5-HT 3 RA + dex (± NK 1 RA) aprepitant PO if PO used Day 1 ± dex 17 Hesketh, PJ et al Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update Summary . National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018 Journal of Oncology Practice 2017 13:12, 825-830
REFER TO MOST UPDATED VERSION OF GUIDELINES: INCLUDING NATIONAL COMPREHENSIVE CANCER NETWORK (NCCN) Type of Emesis, Day 1 Emetic Risk Dex CINV Metoclopramide Low Prochlorperazine 5-HT 3 RA CINV No routine prophylaxis regimen Minimal Radiation Therapy (RT) Granisetron PO daily or ondansetron PO BID ± dex RT – local Granisetron PO daily or ondansetron PO BID/TID ± dex See respective emetic risk of agents TBI Chemo and RT 18 Hesketh, PJ et al Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update Summary . National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018 Journal of Oncology Practice 2017 13:12, 825-830
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