A randomized, double-blind, placebo-controlled study evaluating the efficacy of combination olanzapine, ondansetron and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving doxorubicin plus cyclophosphamide.

Abstract

Since most of Thai cancer patients receiving high emetogenic chemotherapy do not have access to neurokinin-1 (NK-1) receptor antagonists or palonosetron as recommended by international guidelines for chemotherapy-induced nausea and vomiting (CINV) prevention. We decided to evaluate the efficacy of olanzapine with the real-life practice antiemetic drugs ondansetron and dexamethasone, in prevention of CINV resulting from doxorubicin plus cyclophosphamide regimen in early-stage breast cancer patients. In this randomized, double-blind, placebo-controlled trial, we compared olanzapine with a placebo in combination with ondansetron and dexamethasone in early-stage breast cancer patients receiving doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2. The intervention group received olanzapine 10 mg orally while the control group received a matching placebo daily on day 1 through day 4. All patients received ondansetron 8 mg and dexamethasone 20 mg intravenously 30 minutes before chemotherapy administration and then dexamethasone 10 mg daily orally from day 1 through day 4. The primary endpoint was no nausea rate in the early period. The secondary endpoints were no nausea rate in the delayed and overall periods and a complete response (no vomiting and no use of rescue drug). Outcomes were determined by patients' self-reported daily records of episodes of vomiting or retching, use of rescue therapy and daily levels of nausea based on a visual-analogue scale from the first cycle of chemotherapy. A total of 39 female patients were randomized in a 1:1 ratio to receive olanzapine (20 patients) or a matching placebo (19 patients). A significantly greater proportion of patients reported no nausea in the olanzapine group than in the placebo group in both the early period (0-24 hours after chemotherapy) and the overall period (0-120 hours after chemotherapy). Patients who reported no nausea in the early period accounted for 50% and 10.5% in the olanzapine group and in the placebo group respectively (P=0.008). In the overall period, 30.0% and 0% of patients reported no nausea in the olanzapine and placebo groups respectively (P=0.009). In the early period, there was a significantly different complete response rate between two treatment groups; 75.0% in the olanzapine group and 36.8% in the placebo group (P=0.016). Overall treatment-related adverse events were not significantly different between the two study groups except that somnolence was significantly more common in the olanzapine group than in the placebo group. Olanzapine 10 mg combined with ondansetron and dexamethasone was more effective than a placebo in preventing CINV resulting from doxorubicin plus cyclophosphamide in early-stage breast cancer patients, especially in the first 24 hours after chemotherapy administration. The short duration of olanzapine was safe and well tolerated.