Radiation-induced nausea and vomiting remains an important supportive care issue for patients receiving abdominal or pelvic radiotherapy.
Even with standard antiemetic therapy, many patients continue to experience nausea, vomiting, reduced oral intake, appetite loss, sleep disturbance, anxiety, and decreased quality of life during treatment.
A new phase III randomized placebo-controlled trial published in Radiotherapy and Oncology evaluated whether repurposing olanzapine could improve prevention of radiation-induced nausea and vomiting during abdominal-pelvic radiotherapy.
The study found that adding low-dose olanzapine to standard ondansetron significantly reduced nausea, vomiting, and rescue medication use during treatment.
Why This Study Matters
Radiation-induced nausea and vomiting is common during abdominal and pelvic radiotherapy.
The problem is especially relevant for patients receiving larger treatment fields or concurrent chemoradiation, where gastrointestinal symptoms can affect treatment tolerance and daily functioning.
Standard antiemetics, including 5-HT3 receptor antagonists such as ondansetron, can help but do not fully prevent symptoms in many patients.
Olanzapine is already used in chemotherapy-induced nausea and vomiting because it acts on several receptors involved in the emetic pathway, including dopamine, serotonin, and histamine receptors.
This trial tested whether the same drug could be useful in radiotherapy-induced nausea and vomiting.
Study Design
This was a prospective, double-blind, phase III randomized placebo-controlled study conducted in India. Adults with cancer planned for at least 15 fractions of abdominal or pelvic radiotherapy were eligible. Patients were randomized to one of two arms: Standard arm: ondansetron 4 mg twice daily plus placebo.
Experimental arm: ondansetron 4 mg twice daily plus olanzapine 5 mg once daily. Olanzapine was given 30 minutes before radiotherapy.
The primary endpoint was complete control of nausea during radiotherapy. Secondary endpoints included control of vomiting, rescue medication use, toxicity, anxiety, depression, sleep, and quality of life.
Patient Population
Between February 2022 and August 2024, 683 patients were screened. A total of 306 patients were randomized, and 301 patients were included in the efficacy analysis. There were 153 patients in the ondansetron plus placebo arm and 148 patients in the ondansetron plus olanzapine arm.
Baseline characteristics were comparable between the two groups. The most common cancer types were rectal cancer and prostate cancer.
More than half of patients in both arms received concurrent capecitabine-based chemotherapy. Most patients received pelvic radiotherapy, and most were treated with image-guided radiotherapy.
Key Results
The addition of olanzapine produced a large reduction in nausea during radiotherapy.
No or minimal nausea was reported in 85.8% of patients in the olanzapine arm compared with 16.3% in the placebo arm. nGrade 2 or higher nausea was much lower with olanzapine: 7.4% versus 67.3% with placebo.
The benefit was particularly notable in patients receiving concurrent chemoradiation. Among patients receiving concurrent chemotherapy, no nausea was reported in 87% of the olanzapine arm compared with 6% of the placebo arm.
In rectal cancer, grade 2 or higher nausea occurred in 2.8% of patients receiving olanzapine compared with 85.7% in the placebo arm.
Vomiting Control
Olanzapine also improved vomiting control. No vomiting was reported in 95.9% of patients in the olanzapine arm compared with 74.5% in the placebo arm.
Grade 2 or higher vomiting occurred in 1.4% of patients receiving olanzapine compared with 7.8% receiving placebo.
Rescue antiemetic therapy was required less often with olanzapine, 1.4% versus 7.8%. Weekly vomiting rates remained lower with olanzapine throughout treatment, with significant differences emerging from the second week onward.
Safety
Olanzapine was generally well tolerated at the 5 mg daily dose.
No grade 4 or grade 5 toxicities were observed. Grade 1 adverse events seen more often in the olanzapine arm included drowsiness, orthostatic hypotension, dysarthria, and elevated prolactin.
Drowsiness occurred in about 10% of patients receiving olanzapine. Constipation was common in both groups, likely reflecting the use of antiemetics and pelvic radiotherapy.
The study also reported longer sleep duration in the olanzapine arm, suggesting a possible additional supportive care benefit for patients undergoing radiotherapy.
Anxiety, Depression, and Quality of Life
Anxiety and depression scores improved significantly in the olanzapine arm.In contrast, anxiety and depression scores worsened in the placebo arm during treatment.
Mean global health status quality-of-life scores after radiotherapy were not significantly different between the two groups. The authors noted that quality-of-life assessment was not the main objective of the present paper.
Clinical Interpretation
This trial provides high-level evidence supporting olanzapine as an effective addition to standard antiemetic therapy for patients receiving abdominal or pelvic radiotherapy.
The benefit was most striking for nausea, which is often harder to control than vomiting and can substantially affect nutrition, comfort, and treatment experience.
The results are especially relevant for patients receiving concurrent chemoradiation and for those treated to larger abdominal or pelvic fields.
A low dose of 5 mg daily appeared effective and was associated mainly with mild, manageable adverse effects.
Limitations
The study was conducted at a single tertiary care teaching hospital.
The main cancer cohorts were rectal and prostate cancer, while stomach and pancreatic cancer numbers were small and grouped together for exploratory analysis. The study was not powered to evaluate differences by radiotherapy technique.
Long-term effects were not assessed because they were not study endpoints. Despite these limitations, the randomized, double-blind, placebo-controlled design makes the findings clinically important.
Clinical Takeaway
Adding olanzapine 5 mg once daily to ondansetron significantly reduced radiation-induced nausea and vomiting during abdominal-pelvic radiotherapy.
The regimen also reduced the need for rescue therapy and was generally well tolerated.
For patients receiving abdominal or pelvic radiotherapy, especially with concurrent chemotherapy, low-dose olanzapine may offer a practical way to improve supportive care during treatment. This study supports broader consideration of olanzapine in the prevention of radiotherapy-induced nausea and vomiting.
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