Low-dose olanzapine as good as megestrol acetate for cancer anorexia–cachexia syndrome

For vulnerable cancer patients undergoing chemotherapy, treatment with low-dose olanzapine works just as well as megestrol acetate in terms of promoting appetite and weight gain, as shown in a study.

The primary endpoint of the proportion of patients achieving at least a 5-percent weight gain after 12 weeks of intervention was 46.8 percent with low-dose olanzapine vs 40.3 percent with megestrol acetate arms (p=0.41). [ESMO Asia 2025, abstract 820MO]

Although the proportion was higher in the low-dose olanzapine arm, the difference was not statistically significant, noted first study author Dr Abhirup Chanda from Max Super Speciality Hospital in Saket, Delhi, India.

Appetite improvements, as measured objectively using the Functional Assessment of Anorexia Cachexia Therapy – Anorexia Cachexia Subscale (FAACT-ACS >37) and subjectively using a 10-point Numerical Rating Scale (NRS; a ≥3-point improvement) occurred in a similar proportion of patients in the two treatment arms.

A total of 27.3 percent of patients in the low-dose olanzapine arm and 26 percent in the megestrol acetate arm had a FAACT-ACS score of >37 (p=0.85). For the subjective measure, 41.6 percent and 36.4 percent in the respective treatment arms had a ≥3-point improvement on the NRS (p=0.50). All values, while numerically higher in the low-dose olanzapine arm, were not significant, according to Chanda.

These findings demonstrate that low-dose olanzapine has an efficacy comparable to that of megestrol acetate, which is often prescribed to improve appetite in patients with cancer anorexia-cachexia syndrome, Chanda said.

In terms of side effect profile, Chanda emphasized that while the adverse effects were not tracked in the study, historical data provide evidence that olanzapine is better. “Megestrol acetate, a steroid congener, is associated with several side effects, including hyperglycaemia and venous thromboembolism episodes, when given during chemotherapy.”

Beyond its favourable tolerability, olanzapine “has additional antiemetic utility and convenient once-daily dosing schedule. [It is also] around 15 times cheaper than megestrol acetate,” he said.

The opportunity to use one drug to promote weight gain and address chemotherapy-induced nausea/vomiting, along with the low cost, makes olanzapine a viable and cost-effective option for cancer care in low- and middle-income countries, according to Chanda.

The study included 154 patients with newly diagnosed locally advanced or metastatic gastric, hepato-pancreatico-biliary, or lung cancer. These patients were alternatively assigned to receive either low-dose olanzapine (2.5 mg) once daily at bedtime (n=77) or megestrol acetate (160 mg) thrice daily (n=77) alongside chemotherapy for 12 weeks.

The proportion of patients aged ≥60 years was 49.4 percent in the low-dose olanzapine arm and 54.5 percent in the megestrol acetate arm, and there were more male patients in both treatment arms (55.8 percent and 62.3 percent, respectively). Overall, most patients had an ECOG PS score of 0-1 (79.2 percent–87 percent) and a metastatic disease (80.5 percent–84.4 percent). The most common diagnosis was pancreatic cancer (32.5 percent–36.4 percent).