Addition of thalidomide for prevention of chemotherapy-induced nausea and vomiting in the second cycle after the failure of four-drug regimen in the first cycle.

Abstract

Four-drug antiemetic prophylaxis achieves emesis control in 70-90% of patients receiving highly emetogenic chemotherapy (HEC). However, less than half achieve control of nausea. We added thalidomide to OAOD (ondansetron, aprepitant, dexamethasone, and olanzapine) to try and improve nausea control. Adults (> 18 years) who had failed ("any nausea" in 0-120 h after HEC) OAOD prophylaxis in cycle 1, were randomly assigned to thalidomide (T = 50 mg OD for 5 days) + OAOD or placebo (P) + OAOD in cycle 2. The primary endpoint was the proportion of patients achieving "no nausea" in 0-120 h from chemotherapy in the second cycle. A sample size of 50 (including dropouts) would be able to detect 30% "no nausea" in the T arm (β = 80%, α = 0.05). We enrolled 105 patients in cycle 1 and randomized 49 patients (25 thalidomide/ 24 placebo; median age 45(30-60) years; all anthracycline/ cyclophosphamide for breast cancer). The addition of thalidomide did not improve the proportion with "no nausea" in the overall (0-120 h) [T (16%) vs. P (21%); p = 0.72)], acute (0-24 h) (32% vs. 25%, p = 0.58), and delayed (24-72 h) (32% vs. 25%, p = 0.46) periods. Severe nausea (VAS ≥ 7) in the delayed period was reduced (T = 4% vs. P = 30%, p = 0.02). Sedation and dizziness were not increased, but mild constipation was higher with thalidomide [T (84%) vs. P (58%), p = 0.047)]. The addition of thalidomide to standard 4-drug CINV prophylaxis in cycle 2 did not improve nausea control among patients who "failed" the 4-drug regimen in cycle 1.Trial Registration: The trial was registered ( www.ctri.nic.in ; CTRI/2021/08/035980).