Background: Cancer anorexia-cachexia syndrome (CACS) is a multifactorial metabolic condition prevalent among patients with advanced malignancies and often exacerbated by chemotherapy or radiotherapy (RT). While pharmacologic options such as megestrol and corticosteroids are available, their use is limited by cost or adverse effects. Olanzapine, a second-generation antipsychotic, has recently been recommended by American Society of Clinical Oncology for managing CACS, but real-world data remain scarce.

Methods: This retrospective cohort study was conducted at a tertiary oncology centre in West Bengal, India, and included patients aged 18–70 years with any solid malignancy and severe anorexia, receiving chemotherapy, RT or palliative care. All patients were treated with low-dose Olanzapine (2.5 mg/day) for 12 weeks. Data were extracted from medical records for the period between 1 January 2024, and 31 January 2025.

Results: Fifty patients met the inclusion criteria. The median age was 44.5 years and 82% had Stage III/IV disease. Of these, 82% (n = 41/50) reported improvement in anorexia symptoms, 82% maintained or gained weight and 16% (n = 8/50) gained at least 1 kg. Among 24 patients with refractory nausea, 50% reported symptomatic relief. No adverse events attributable to Olanzapine were documented.

Conclusion: Low-dose olanzapine (2.5 mg/day) is an effective, well-tolerated and cost-efficient option for the management of cancer-related anorexia and nausea in real-world clinical settings. Its use may be particularly beneficial in resource-limited environments and should be considered as a first-line pharmacologic intervention for CACS. Further prospective studies are warranted.