Phase III randomized placebo-controlled trial on repurposing olanzapine for prevention of radiotherapy induced nausea and vomiting (RINV): CTRI/2022/01/039723.

Abstract

Prospective, double-blind, phase III randomized placebo-controlled study evaluated the efficacy of olanzapine in preventing RINV during abdominal-pelvic radiation therapy. Patients receiving abdominal/pelvic RT without prior radiation were randomized to receive either olanzapine 5 mg or placebo once daily, alongside standard ondansetron (4 mg BID). Primary endpoint was nausea prevention; secondary endpoints included emesis control, rescue medication use, toxicity, anxiety, depression, and quality of life (QOL). Between Feb 2022 and Aug 2024, 301 patients were randomized to 5HT3 + placebo (n = 153) or 5HT3 + olanzapine (n = 148). Baseline characteristics were comparable. During radiation therapy treatment, proportion of patients with 'no/ minimal' nausea events in 5HT3 + Olanzapine arm was 85.8% and in 5HT3 + placebo arm was 16.3% (p < 0.001) respectively. Similarly, 'no/minimal' vomiting events reported in 5HT3 + Olanzapine arm was 95.9% and in 5HT3 + placebo arm was 74.5% (p < 0.001) respectively. Vomiting episodes ≥ 15 were more in 5HT3 + placebo (9.2%) than 5HT3 + olanzapine (2%; p = 0.001). Rescue therapy required in 7.8% (placebo) & 1.4% (olanzapine) (p = 0.008). Grade ≥ 2 nausea was 67% (placebo) vs 7.4% (olanzapine) (p = 0.001). In rectal cancer, grade ≥ 2 nausea in placebo & olanzapine arms were 85.7% & 2.8% (p = 0.001). Nausea in concurrent chemoradiation was higher in placebo 82(94.3%) vs olanzapine 10(12.6%) (p < 0.001). Grade ≥ 2 vomiting occurred in 7.8% (placebo) and 1.4% (olanzapine) (p = 0.001). Vomiting in concurrent chemoradiation was higher in placebo 28(32.2%) vs olanzapine 5(6.3%) (p < 0.001). Adverse reactions (grade 1) in olanzapine arm included drowsiness (p < 0.001), dysarthria (p = 0.003), orthostatic hypotension (p < 0.001). No grade 4/5 toxicity observed. Anxiety and depression reduced significantly (p < 0.001). Mean EORTC GHS QOL score post-RT: 61.6 ± 8.6 (standard) vs 62.9 ± 9.2 (experimental) (p = 0.235). Adding olanzapine 5 mg with standard antiemetics significantly reduced RINV during abdominal-pelvic radiation therapy.