Efficacy of olanzapine combination in prevention of nausea & vomiting in highly emetogenic chemotherapy

Abstract

Background: Chemotherapy Induced Nausea and Vomiting (CINV) is a common phenomenon and various modalities are being looked to reduce this adverse event. Though these modalities better control emesis, nausea is still a problem that is not optimally controlled, thus requiring newer methods to control the same. Methods: In this study, various combinations of Olanzapine (O), Aprepitant (A), Dexamethasone (D) and 5‐HT3 Antagonist (H) were randomized to three groups ‐ standard (AHD), combined (AHDO) & olanzapine (HDO) and compared for efficacy to address the problem of CINV. Patients who had never had any previous chemotherapy and receiving cisplatin, cyclophosphamide‐doxorubicin & any other Highly Emetogenic Chemotheraphy (HEC) as per guidelines were enrolled. The standard doses of the concomitant drugs were administered before and after chemotherapy. The two groups receiving Olanzapine were administered 10 mg orally daily on days 1 through 4. Nausea prevention & complete response (no emesis, no use of rescue medication) were primary end points. The toxicity profile and quality of life were secondary end points. Results: Total of 209 subjects were included in this study (68 in standard (A), 70 in combined (B) & 71 in olanzapine (C) arm). The proportion of patients with no chemotherapy induced nausea was significantly greater in group B than in C & A arm for first 24 hours after chemotherapy (80% (B) v/s 63.23% & 58.9% (A&C); p<0.01), the delayed period (25‐120 hours) after chemotherapy (75.71% (B) v/s 59.23% & 64% (A&C); p<0.05) and the overall 120‐hour period (74% (C) v/s 48% & 52% (A&C); p<0.01). The complete response rate for vomiting was also significantly increased with group B during the three periods ‐ (85.71% (B) v/s 69.1% & 62% (A&C); p<0.05), (81%(B) v/s 70.5% & 68.3% (A&C); p=0.09, and 77.14% (B) v/s 60.29% & 59.3% (A&C); p<0.05) respectively. Although there were no significant differences between QTc intervals & blood sugar levels, 5% patients receiving olanzapine had increased sedation (grade 2). Conclusions: Addition of Olanzapine to the standard arm significantly improved nausea prevention, as well as the complete response for vomiting. This modality may be further studied to determine its efficacy in lower doses so as to negate the effect of sedation.