Melatonin and Cisplatin-Associated Skeletal Muscle Wasting and Atrophy: Mechanistic Rationale, Current Evidence, and Research Gaps

Cisplatin causes skeletal muscle wasting in tumor-free rodents, reducing muscle mass, myofiber size and, where measured, strength. This critical narrative review appraises that phenotype and its mechanistic basis. Tumor-bearing models show that the loss also occurs under tumor burden, but most cannot separate drug from tumor effects. Melatonin influences mitochondrial, redox, regenerative, and structural outcomes in skeletal muscle under non-cisplatin conditions. Direct melatonin–cisplatin evidence is limited to pretreatment studies in C2C12 cells from one research group. No in vivo melatonin-plus-cisplatin skeletal-muscle study and no clinical study of melatonin against cisplatin-associated muscle loss were identified in searches through 22 September 2026. Biological plausibility is supported, but protection has not been demonstrated. A controlled tumor-free study would provide a more interpretable test of whether melatonin protects skeletal muscle during cisplatin exposure. Translational validation would then require a separate tumor-bearing study testing whether protection persists under tumor burden and whether cisplatin’s antitumor activity is preserved.