Carbamazepine for the prevention of chemotherapy-induced nausea and vomiting: A pilot study using the Simon's optimal two-stage design.

Abstract

e20699 Background: Nausea and vomiting have been a major drawback to patients undergoing chemotherapy. Despite standard preventive treatment, chemotherapy-induced nausea and vomiting (CINV) still occurs in approximately 50% of patients. Because of its high cost, this treatment is unavailable in centers where health assistance is provided by the government. As an effort to ameliorate prevention of CINV at lower costs, we studied the efficacy of the addition of carbamazepine to a regimen of corticosteroid plus 5-hidroxitriptamine-3 receptor antagonist for prevention of CINV as well as its side effects and influence on patients’ quality of life. Methods: This is a prospective open label phase II nonrandomized study carried out in a Brazilian public Oncology service. Patients scheduled to receive the first cycle of highly emetogenic chemotherapy were continuously recruited. Besides the current standard antiemetic treatment, patients received carbamazepine, p.o., according to the following schedule: 200 mg QD on the third day before chemotherapy; 200 mg BID on the second day before chemotherapy; 200 mg TID from one day before until the fifth day after chemotherapy. Considering sparse evidence about the anticonvulsants’ efficacy in CINV prevention, we adopted Simon’s optimal two-stage design which should include 43 patients unless overall complete prevention was not achieved in 9 out of the first 15 entries. Functional Living Index-Emesis (FLIE) questionnaire was used to measure impact on quality of life. Results: None of ten studied patients (0%) had overall complete prevention and nine needed rescue medication. Three quitted carbamazepine therapy because of somnolence and vomiting before chemotherapy infusion. Seven were able to take medication for the entire period and none were responsive, so the study was closed. There was no impact on patients´ quality of life. Conclusions: Carbamazepine was not effective for prevention of CINV and should not be used for this purpose out of experimental settings. The Simon optimal design allowed us to reach this data and stop the trial for futility, minimising the number of patients possibly exposed to an inactive agent.