Olanzapine May Prevent Radiation-Induced Nausea and Vomiting

Safety data from the trial revealed that among patients assigned to receive 5 mg of olanzapine vs placebo, nausea occurred in 14.2% and 83.6%, respectively.

The addition of olanzapine (Zyprexa) to standard antiemetics may safely and effectively prevent radiation-induced nausea and vomiting in patients receiving abdominal/pelvic radiotherapy or concurrent chemoradiation with low-emetogenic oral capecitabine, according to data from a phase 3 placebo-controlled trial presented at the 2025 American Society of Clinical Oncology Annual Meeting.

Safety data from the trial revealed that among patients assigned to receive 5 mg of olanzapine (n = 148) vs placebo (n = 153), nausea occurred in 14.2% and 83.6%, respectively (P < .001). Additionally, the incidence of grade 2 or greater nausea was 67.3% vs 7.4% with placebo vs olanzapine (P < .001).

Additionally, vomiting was also reduced with olanzapine; 25.5% of the placebo group and 4.1% of the experimental group experienced any-grade vomiting (P < .001). Furthermore, the incidence of grade 2 or higher vomiting was 7.8% vs 1.3% in each respective arm. Further data showed that the addition of olanzapine reduced the total number of vomiting episodes among patients receiving radiotherapy, with 16.3% of the standard group experiencing 1 to 15 episodes vs 2.0% of the experimental group (P = .003); 9.2% vs 2.0% of each arm experienced more than 15 episodes (P = .002).

The incidence of grade 2 or higher nausea was also significantly lower for patients across a variety of cancer types. In patients with endometrial cancer, 85.7% of the placebo group and 2.8% of the experimental group experienced grade 2 or higher nausea (P < .001). The respective rates for endometrial, stomach/pancreatic, and prostate cancers were 92.9% vs 0% (P < .001), 100% vs 40% (P = .006), and 19.1% vs 8.7% (P = .018).

“The addition of 5 mg olanzapine to standard ondansetron therapy is found to be safe and effective for preventing nausea and vomiting in patients receiving abdominal/pelvic radiation therapy and those undergoing concurrent chemoradiation with low-emetogenic oral capecitabine,” Meenu Vijayan, MPharm, assistant professor at the Amrita School of Pharmacy, said in the presentation. “Our study was a single-center study. Future studies involving multiple centers and a large number of patients are recommended to corroborate our findings.”

Patients 18 years or older who were receiving abdominal/pelvic radiotherapy and were previously radiotherapy naive were randomly assigned to receive 4 mg of twice-daily ondansetron (Zofran) and either 5 mg of oral daily olanzapine or matching placebo. The study assessed efficacy and safety using the Common Terminology Criteria for Adverse Events scale, including a nausea and vomiting diary; anxiety and depression using the Hamilton Rating Scale; and quality of life (QOL) using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30.

Patients in the standard and experimental groups, respectively, had a mean age of 63.82 (SD, 10.87) vs 62.32 (SD, 10.47). Additionally, 58.2% vs 62.8% were males and 67.3% vs 70.3% had comorbidities. Furthermore, 18.3% vs 19.6% had a history of smoking, 24.8% vs 23% had a history of alcohol, and 50.3% vs 54.7% had a family history of cancer in respective groups. In total, 56.9% vs 53.4% received concurrent capecitabine and 30.7% vs 31.1% received hormone therapy.

The most common cancer types in the standard and experimental groups included rectal cancer (50.3% vs 48.6%), prostate cancer (30.7% vs 31.1%), and endometrial cancer (9.2% vs 9.5%). The most common type of radiotherapy was image-guided radiation therapy (88.9% vs 83.1%), and the most common radiotherapy site was the pelvic area (91.5% vs 93.2%). Patients in each group received a mean dose of 222.58 Gy daily (SD, 40.691) vs 222.01 Gy daily (SD, 40.137), with a mean duration of 23.67 days (SD, 3.789) vs 23.76 days (SD, 3.420).

Additional findings from the trial revealed that treatment with olanzapine reduced mean anxiety scores vs placebo (P < .001). A similar trend was observed for mean depression scores (P < .001). Additionally, mean changes in QOL score in the functional scale from baseline to radiotherapy universally favored the experimental, particularly for emotional functioning (P < .001). This trend was observed in the symptom scale as well, with significant improvements noted in nausea/vomiting, insomnia, and loss of appetite (all P < .001).

Reference

Vijayan M, Nair H, MP N, VS S, Dutta D. Phase III randomized placebo-controlled trial on repurposing olanzapine for prevention of radiotherapy-induced nausea and vomiting (RINV): CTRI/2022/01/039723. J Clin Oncol. 2025;43(suppl 16):12001.