Background: Chemotherapy Induced Nausea and Vomiting (CINV) is a major problem for all cancer patients. 5-hydroxytryptamine 3 (5-HT3)-receptor antagonists or serotonin antagonists used along with dexamethasone is the most widely used antiemetic regimen in chemotherapy. But the best drug of the different serotonin antagonists, which is both efficacious and economic, remains a matter of debate.
Aims & Objectives: To compare the relative efficacies and safeties of ondansetron, granisetron and palonosetron, when used along with equal dose of dexamethasone, in moderately to highly emetogenic chemotherapy by a double blind, randomized controlled trial in order to obtain the most potent and cost effective drug.
Methods: 1213 adult patients, 487 on highly and 726 on moderately emetogenic chemotherapy, admitted in various departments of a teaching hospital in India from November 05, 2007 to September 30, 2009 were included in the study. Patients were randomly assigned to receive ondansetron 8 mg or granisetron 3mg or palonosetron 0.75 mg (single dose), 30 min before receiving chemotherapy, along with 16 mg of intravenous dexamethasone on Day 1 and 4mg on Day 2 and 3. The observation period started with the initiation of chemotherapy (0 h) and continued for 24 h after completion of the chemotherapy for acute emesis and up to Day 5 for delayed nausea and vomiting.
Results: For highly emetogenic regimens, 52 of 64 patients (81.2%) had complete response during the acute phase in palonosetron group compared with 181 of 237 patients (76.4%) in the ondansetron group and 130 of 186 patients (69.9%) in granisetron group. During the delayed phase, 41 patients (64%) had complete response in the palonosetron group compared with 133 patients (56.1%) in the ondansetron group and 114 patients (61.2%) in granisetron group. For moderately emetogenic regimens, 86 of 93 patients (92.5%) had complete response during the acute phase in palonosetron group compared with 291 of 379 patients (76.8%) in the ondansetron group and 210 of 254 patients (82.6%) in granisetron group. During the delayed phase, 63 patients (67.7%) had complete response in the palonosetron group compared with 216 patients (57%) in the ondansetron group and 162 patients (63.8%) in granisetron group. Main treatment related side effects were constipation and elevation of liver enzymes which was comparable for all the 3 drugs.
Conclusion: When administered with dexamethasone before chemotherapy, although palonosetron is found to be more efficacious, cost wise ondansetron may be preferred in highly emetogenic regimens, although palonosetron requires only a single dosing. However in moderately emetogenic regimens, granisetron outshines ondansetron and is further outshined by palonosetron in both acute and delayed emesis and thus the decision should be taken as per patient profile.
Study Limitations: The study has fewer numbers of patients taking palonosetron due to financial limitations of the patients, which is present in any developing country. Although we have compared the cost and availability of the 3 drugs, a detailed cost analysis could not be done due to paucity of resources.