A randomized, open-label, phase II trial of short-term combination pharmacotherapy in patients receiving cytotoxic chemotherapy for solid tumors.

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Background: Patients from resource-limited settings often tolerate standard chemotherapy poorly, resulting in dose reductions, treatment delays, and hospitalizations. Baseline malnutrition, anorexia, and cancer cachexia are key contributors and frequently worsen during systemic therapy. Practical strategies to improve nutritional status and chemotherapy tolerance in this population remain limited. We evaluated short-term fixed-dose combination pharmacotherapy to improve weight, appetite, and tolerance to chemotherapy. Methods: This randomized, open-label phase 2 study enrolled 91 patients with locally advanced solid cancers and a baseline body mass index below 18 kg/m². Patients were randomized to receive fixed-dose combination pharmacotherapy consisting of megestrol acetate 800 mg per day and olanzapine 5 mg per day or placebo for up to 6 weeks prior to and during chemotherapy. Primary endpoints were weight gain, improvement in appetite, and tolerance to chemotherapy, defined as the absence of grade 3 or higher hematological or non-hematological toxicities according to CTCAE criteria. Appetite and nutritional status were assessed using the Visual Analog Scale (VAS) and Subjective Global Assessment (SGA). Results: Patients in the intervention arm demonstrated significantly greater weight gain and improved appetite compared with the placebo arm. Eighty percent of patients receiving combination pharmacotherapy achieved a weight gain of at least 5 percent from baseline within 6 weeks, with a median time to target weight of 4 weeks, whereas no patients in the placebo arm achieved similar weight gain (p value < 0.01). Conversely, 8 patients in the placebo arm experienced weight loss of 5 percent or more, compared with none in the intervention arm (p = 0.001). Significant improvements in Visual Analog Scale and Subjective Global Assessment scores were observed in the intervention group compared with placebo (p = 0.001 for both). Grade 3 or higher hematological toxicities occurred in 7 patients in the placebo arm, while no such events were observed in the intervention arm (p = 0.046). Conclusions: This study highlights the potential of this low cost; novel pharmacological strategy to mitigate malnutrition, enhance chemotherapy tolerance, and improve quality of life in cancer patients from resource-limited settings.