Significant weight gain benefits of nanocrystalline megestrol acetate for patients with cancer anorexia-cachexia syndrome.

Background: Cancer anorexia-cachexia syndrome (CACS) is a multifactorial syndrome characterized by weight loss and muscle wasting that leads to impaired physical function, decreased tolerance to anticancer therapies, and reduced survival rates. Megestrol acetate (MA) is an important pharmacological intervention for CACS. Nanocrystalline MA (MA-ES), leveraging nanocrystal technology, enhances bioavailability and absorption rates. Previous research has demonstrated that MA-ES could result in a more significant weight increase than non-MA-ES. However, its efficacy and safety in Chinese patients with cancer require further evaluation and validation in real-world clinical settings. The purpose of this study was to evaluate the therapeutic efficacy and safety of MA-ES and MA tablets in hormone-insensitive patients with CACS.

Methods: This prospective, multi-cohort, multicenter, real-world clinical study compared MA-ES and MA tablets in terms of efficacy and safety for hormone-insensitive patients with CACS (excluding breast cancer, endometrial cancer, and prostate cancer). The MA-ES group received 5 mL/day (625 mg/day), while the MA tablet group received 800 mg/day. CACS patients who completed three cycles of MA-ES at 5 mL/day or MA tablets at 800 mg/day were included in the propensity score matching (PSM) analysis (one cycle was defined as 28 days, with ≥21 days considered as completion of one cycle). PSM (1:2 ratio, caliper width 0.1) was used to mitigate the confounding factors. Patients were treated for three consecutive cycles, with each cycle lasting 4 weeks. The primary endpoint was the change in body weight from baseline at 12 weeks. Additionally, appetite, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scores, and safety were also evaluated. The standardized mean differences (SMDs) before and after PSM were calculated to examine the balance of covariate distributions between two groups.

Results: Between October 15, 2024 and February 28, 2025, 126 patients met the screening criteria and were enrolled in the analysis, with 76 in the MA-ES group and 50 in the MA tablet group. SMD of each matched variable was less than 0.10. At week 12, the MA-ES group exhibited an average weight gain of 4.49 kg, significantly higher than the 2.10 kg observed in the MA tablet group, with a mean difference of 2.39 kg (95% confidence interval: 1.33-3.45; P<0.001). Furthermore, at week 12, the MA-ES group demonstrated significantly greater proportions of participants with improved appetite (81.6% vs. 42.0%; P<0.001) and enhanced global health status (P<0.001).

Conclusions: MA-ES administered at 625 mg/day for over three cycles may offer superior weight gain benefits compared to the conventional MA tablets at 800 mg/day in hormone-insensitive patients with CACS. Moreover, MA-ES appears to provide more significant advantages in improving appetite and overall quality of life. Therefore, MA-ES may offer better clinical benefits compared to MA tablets for CACS patients.