Add-on olanzapine prevents RT-induced nausea, vomiting

In patients undergoing abdominal-pelvic radiation therapy (RT), treatment with olanzapine along with an antiemetic medication leads to a substantial decrease in RT-induced nausea and vomiting (RINV), with no serious adverse effects, reports a study presented at ASCO 2025.

Olanzapine also alleviates insomnia, appetite loss, anxiety, and depression, thus improving quality of life (QOL) in patients receiving concurrent chemoradiation with low emetogenic oral capecitabine, according to lead study author Dr Meenu Vijayan from Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, Kerala, India.

“The addition of 5-mg olanzapine to standard ondansetron therapy is safe and effective for preventing nausea and vomiting in patients receiving abdominal/pelvic RT and those undergoing concurrent chemoradiation with low-emetogenic oral capecitabine,” she said. [ASCO 2025, abstract 12001]

In this phase III, double-blind, placebo-controlled trial, Vijayan and her team screened 683 patients (aged >18 years) undergoing RT (abdominal/pelvic, with no prior RT history) between February 2022 and August 2024. Of these, 301 were randomized to receive olanzapine 5 mg (n=148) or placebo (n=153) daily, along with standard care (ondansetron 4 mg twice daily).

Nausea prevention was the main endpoint, while no emesis, no rescue medications, toxicity, and QOL were secondary. Statistical analysis was done using Pearson chi-square test and independent t-test.

In the olanzapine arm, the mean age of participants was 62.3 years, and 37 percent were female. Of the patients, 72 (49 percent) had rectal cancer, 46 (31 percent) prostate cancer, 14 (9.5 percent endometrial cancer, and five (3.4 percent) pancreatic cancer.

In the placebo arm, the mean age was 63.8 years, with 42 percent female patients. Seventy-seven (50 percent) had rectal cancer, while 47 (31 percent) had prostate cancer, 14 (9 percent) endometrial cancer), and nine (6 percent) pancreatic cancer.

Image-guided RT was performed in 89 percent of patients in the placebo arm and 83 percent in the olanzapine arm. In addition, concurrent chemotherapy was administered to 57 percent and 53 percent of patients in the respective groups.

Nausea, vomiting

Significantly more patients on olanzapine than on placebo were spared from nausea (85.8 percent vs 16.3 percent; p<0.001) and vomiting (95.9 percent vs 74.5 percent; p<0.001) during RT. On the other hand, more patients on placebo vs olanzapine experienced >15 total number of vomiting episodes (9.2 percent vs 2 percent; p=0.002) and required rescue therapy (7.8 percent vs 1.4 percent; p=0.008).

In addition, grade ≥2 nausea (67 percent vs 7.4 percent; p=0.001) and vomiting (7.8 percent vs 1.4 percent; p=0.001) occurred more frequently among placebo-treated patients. Among rectal cancer patients, grade ≥2 nausea rates were 85.7 percent vs 2.8 percent (p=0.001), respectively, while the corresponding rates among those with prostate cancer were 19 percent vs 9 percent (p=0.018).

Significant adverse reactions also occurred in the olanzapine arm, and these included grade 1 drowsiness (p<0.001), dysarthria (p=0.003), and orthostatic hypotension (p<0.001). 

QOL benefits

In patients treated with olanzapine, the mean anxiety score improved from 13.4 before RT to 11.1 after RT (p<0.001). However, the opposite was true for those given placebo, with mean anxiety scores of 13.2 and 14.5 (p<0.001), respectively. For depression, the corresponding mean scores before and after RT were 11.9 and 9.7 in the olanzapine arm (p<0.001) and 11.9 and 13.7 in the placebo arm (p<0.001).

Patients on olanzapine also had more sleep hours compared with those on placebo (8.4 vs 5.29 h; p<0.001). QOL score from baseline to end of RT showed improvements in emotional function, nausea/vomiting, insomnia, and loss of appetite (p<0.001 for all) in the olanzapine arm.

At RT completion, the mean EORTC GHS QOL score was 62.9 in the olanzapine group and 61.6 in the placebo group (p=0.235).

“Olanzapine 5 mg is a safe and effective add-on therapy to standard antiemetics for preventing RINV,” Vijayan said.

“Future studies involving multiple centres and a large number of patients are recommended to corroborate our findings,” she added.