A phase 3 randomized placebo-controlled trial has demonstrated that adding olanzapine to standard antiemetic therapy significantly reduces radiation-induced nausea and vomiting (RINV) in patients receiving abdominal or pelvic radiotherapy. The findings, presented at the 2025 American Society of Clinical Oncology Annual Meeting, suggest a new therapeutic approach for managing one of radiation therapy's most distressing side effects.
Dramatic Reduction in Nausea and Vomiting
The trial enrolled 301 patients who were randomly assigned to receive either 5 mg of daily olanzapine (n=148) or placebo (n=153), both combined with standard ondansetron therapy. The results showed striking differences between treatment groups, with nausea occurring in only 14.2% of olanzapine-treated patients compared to 83.6% of those receiving placebo (P <.001).
The benefits extended to severe symptoms as well. Grade 2 or greater nausea affected 7.4% of patients in the olanzapine group versus 67.3% in the placebo group (P <.001). Similarly, any-grade vomiting occurred in 4.1% of olanzapine-treated patients compared to 25.5% of those receiving placebo (P <.001).
The frequency of vomiting episodes was also substantially reduced. Among patients experiencing vomiting, 2.0% of the olanzapine group had 1 to 15 episodes compared to 16.3% in the placebo group (P = .003). For more severe cases with over 15 episodes, the rates were 2.0% versus 9.2% respectively (P = .002).
Benefits Across Cancer Types
The antiemetic effects of olanzapine were consistent across different cancer diagnoses. In patients with endometrial cancer, grade 2 or higher nausea occurred in 2.8% of the olanzapine group versus 85.7% of the placebo group (P <.001). For stomach and pancreatic cancers, the rates were 40% versus 100% (P = .006), while prostate cancer patients experienced rates of 8.7% versus 19.1% (P = .018).
The study population included patients with rectal cancer (50.3% vs 48.6% in placebo vs olanzapine groups), prostate cancer (30.7% vs 31.1%), and endometrial cancer (9.2% vs 9.5%). Most patients received image-guided radiation therapy (88.9% vs 83.1%) primarily to the pelvic area (91.5% vs 93.2%).
Study Design and Patient Characteristics
Patients aged 18 years or older who were receiving abdominal/pelvic radiotherapy and were previously radiotherapy naïve were eligible for enrollment. All participants received 4 mg of ondansetron twice daily plus either 5 mg of oral daily olanzapine or matching placebo. The study assessed outcomes using the Common Terminology Criteria for Adverse Events scale, patient diaries, the Hamilton Rating Scale for anxiety and depression, and the EORTC QLQ C30 questionnaire for quality of life.
Patient demographics were well-balanced between groups. The mean age was 63.82 years (SD 10.87) in the placebo group versus 62.32 years (SD 10.47) in the olanzapine group. Male patients comprised 58.2% and 62.8% of each group respectively, while 67.3% and 70.3% had comorbidities. Concurrent capecitabine was administered to 56.9% and 53.4% of patients in each group.
Radiation therapy parameters were similar between groups, with mean doses of 222.58 Gy/day (SD 40.691) versus 222.01 Gy/day (SD 40.137) and mean treatment durations of 23.67 days (SD 3.789) versus 23.76 days (SD 3.420).
Additional Quality of Life Benefits
Beyond antiemetic effects, olanzapine treatment provided broader supportive care benefits. Patients receiving olanzapine showed significantly reduced mean anxiety scores compared to placebo (P <.001), with similar improvements observed for depression scores (P <.001).
Quality of life measurements favored the olanzapine group across multiple domains. Emotional functioning showed particular improvement (P <.001), while symptom scale assessments revealed significant benefits for nausea/vomiting, insomnia, and loss of appetite (all P <.001).
Clinical Implications and Future Directions
"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," stated Meenu Vijayan, MPharm, assistant professor at the Amrita School of Pharmacy, who presented the findings.
The researchers acknowledged study limitations, noting that this was a single-center investigation. "Future studies involving multiple centers and a large number of patients are recommended to corroborate our findings," Vijayan emphasized.
The trial represents a significant advancement in radiation oncology supportive care, potentially offering patients a more effective approach to managing RINV through the repurposing of an established psychiatric medication.
