RESUMO
BACKGROUND: Concurrent chemotherapy radiation therapy may result in significant nausea and vomiting. There have been few studies reporting effective interventions for preventing treatment-related nausea and vomiting. OBJECTIVE: To compare olanzapine with fosaprepitant for the prevention of nausea and vomiting in patients receiving concurrent highly emetogenic chemotherapy (HEC) and radiotherapy for locally advanced head and neck or esophageal cancer. METHODS: 120 chemotherapy and radiotherapy naïve patients with head and neck cancer who were receiving concurrent local radiation and cisplatin were randomized to receive either olanzapine or fosaprepitant in combination with palonosetron and dexamethasone for the prevention of chemotherapy- and radiation-induced nausea and vomiting. The olanzapine, palonosetron, dexamethasone (OPD) regimen was 10 mg oral olanzapine , 0.25 mg IV palonosetron, and 20 mg IV dexamethasone before chemotherapy on day 1, and 10 mg/day of oral olanzapine before chemotherapy on days 2-4. The fosaprepitant, palonosetron, dexamethasone (FPD) regimen was 150 mg IV fosaprepitant, 0.25 mg IV palonosetron, and 12 mg IV dexamethasone before chemotherapy on day 1, and 4 mg dexamethasone PO BID, before chemotherapy days 2 and 3. RESULTS: 101 of the 120 patients were evaluable. In 51 patients who received the OPD regimen, the complete response (CR; no emesis, no rescue medication) rate was 88% for the acute period (24 h after chemotherapy), 76% for the delayed period (days 2-5), and 76% for the overall period (0-120 h). In 50 patients who received the FPD regimen, the CR was 84% acute, 74% delayed, and 74% overall (ð > .01 for all periods). Patients with no nausea (0, on a scale 0-10, visual analogue scale) were: OPD: 86% acute, 71% delayed, 71% overall; FPD: 78% acute, 40% delayed, 40% overall (ð > .01 for acute; ð < .01 for delayed and overall) There were no grade 3 or 4 toxicities. CONCLUSIONS: CR was similar for OPD and FPD; nausea in the delayed and overall periods was signifcantly improved with OPD compared with FPD (ð < .01).
RESUMO
PURPOSE: Olanzapine has been shown to be a safe and effective agent for the prevention of chemotherapy-induced nausea and vomiting (CINV). Olanzapine may also be an effective rescue medication for patients who develop breakthrough CINV despite having received guideline-directed CINV prophylaxis. METHODS: A double-blind, randomized phase III trial was performed for the treatment of breakthrough CINV in chemotherapy-naive patients receiving highly emetogenic chemotherapy (cisplatin, ≥ 70 mg/m2 or doxorubicin, ≥ 50 mg/m2 and cyclophosphamide, ≥ 600 mg/m2), comparing olanzapine to metoclopramide. Patients who developed breakthrough emesis or nausea despite prophylactic dexamethasone (12 mg IV), palonosetron (0.25 mg IV), and fosaprepitant (150 mg IV) pre-chemotherapy and dexamethasone (8 mg p.o. daily, days 2-4) post-chemotherapy were randomized to receive olanzapine, 10 mg orally daily for 3 days or metoclopramide, 10 mg orally TID for 3 days. Patients were monitored for emesis and nausea for 72 h after taking olanzapine or metoclopramide. Two hundred seventy-six patients (median age 62 years, range 38-79; 43% women; Eastern Cooperative Oncology Group (ECOG) PS 0,1) consented to the protocol. One hundred twelve patients developed breakthrough CINV and 108 were evaluable. RESULTS: During the 72-h observation period, 39 out of 56 (70%) patients receiving olanzapine had no emesis compared to 16 out of 52 (31%) patients with no emesis for patients receiving metoclopramide (p < 0.01). Patients without nausea (0, scale 0-10, M.D. Anderson Symptom Inventory) during the 72-h observation period were those who took olanzapine, 68% (38 of 56), and metoclopramide, 23% (12 of 52) (p < 0.01). There were no grade 3 or 4 toxicities. CONCLUSIONS: Olanzapine was significantly better than metoclopramide in the control of breakthrough emesis and nausea in patients receiving highly emetogenic chemotherapy.
