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

12001 Background: Prospective placebo controlled randomized study with or without olanzapine, to evaluate its role in reducing RINV in abdominal-pelvic radiation therapy patients. Methods: Phase III, double-blind, placebo-controlled trial in patients undergoing radiotherapy (RT) [Eligibility: >18 yrs, abdominal/pelvic RT, no prior RT history] were randomized to receive 5mg olanzapine or matching placebo daily, along with standard care (ondansetron 4mg twice daily) using simple randomization method. Primary endpoint was nausea prevention. Secondary endpoint was no emesis, no rescue medications, toxicity (CTCAE v5), & QOL. Pearson chi-square test & independent t-test employed for statistical analysis. Results: Between Feb 2022 to Aug 2024, 683 patients were screened & 301 randomized [153 placebo, 148 experimental/olanzapine]. In placebo & experimental arm, mean age was 63.8 years (+/- 10.8) & 62.3 years (+/-10.4), female 42% & 37%, rectal cancer 77(50%) & 72 (49%), prostate 47 (31%) & 46 (31%), endometrial cancer 14 (9%) & 14(9.5%), pancreatic cancer 9(6%) & 5(3.4%) (p=NS). In placebo & experimental arm, Image-guided RT done in 89% & 83%(p=NS), concurrent chemotherapy in 57% & 53% (p=NS). During RT, ‘no nausea’ & ‘no vomiting’ complain in placebo & experimental arms were 16.3 & 85.8% (p= <0.001); 74.5% & 95.9% (p= <0.001). Total number of vomiting episodes >15 times during RT in placebo & experimental arm were 9.2% & 2% (p=0.002). Rescue therapy during RT required in 7.8% placebo &1.4% in experimental arm (p=0.008). Grade≥2 nausea in placebo & in experimental arm 67% & 7.4% (p=0.001), and vomiting 7.8% & 1.4% (p=0.001). In rectal cancer, nausea grade ≥2 in placebo & experimental arm were 85.7% & 2.8% (p=0.001) & in prostate cancer 19% & 9% (p=0.018). In experimental arm, significant adverse reactions (grade 1) included drowsiness (p<0.001), dysarthria (p=0.003), and orthostatic hypotension (p<0.001). Mean anxiety score before & after RT in placebo was 13.2 (+/-2.5) &14.5 (+/-2.4) (p<0.001); in experimental arm 13.4 (+/-2.3) & 11.1 (+/-2.2) (p<0.001); Mean depression score before & after RT in placebo & experimental arm were 11.9 (+/-1.6) & 13.7 (+/-1.8) (p<0.001); 11.9 (+/-1.6) & 9.7 (+/-1.6) (p<0.001). The olanzapine group had more sleep hours/day (8.4 ±1.7 hours vs. 5.29 ±1.13 hours; p<0.001). QOL score from baseline to end of RT showed improvement in emotional function, nausea/vomiting, insomnia, & loss of appetite (all p<0.001) in olanzapine arm. Mean EORTC GHS QOL score at RT completion was 61.6 (+/- 8.6) in placebo arm and 62.9 (+/-9.2) in experimental arm (p=0.235). Conclusions: Adding olanzapine 5mg along with standard antiemetics demonstrated a significant reduction in RINV in patients receiving abdominal-pelvic radiation therapy. Clinical trial information: CTRI NO/2022/01/039723 .