Associations of oxaliplatin dose, lean body mass, and sarcopenia with dose-limiting neuropathy in patients with colorectal cancer

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BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity of oxaliplatin, currently dosed by body surface area (BSA). BSA does not account for differences in lean body mass (LBM) that may influence toxicity. We assessed the independent and interactive effects of oxaliplatin dose, LBM, and sarcopenia on CIPN in colorectal cancer (CRC) patients. METHODS: Data were analyzed from CRC patients treated with adjuvant CAPOX in routine care. CIPN after each cycle was assessed from medical records using CTCAE v5.0; with grade ≥2 CIPN considered dose-limiting. The initial oxaliplatin dose was obtained from health records. LBM was estimated from diagnostic abdominal CT scans, and sarcopenia was defined using sex-specific skeletal muscle index cut-offs. Associations between initial oxaliplatin dose, LBM, and sarcopenia with time to first grade ≥2 CIPN were estimated using Cox-regression. Stratified analyses by LBM and sarcopenia were conducted to assess whether they modified the association between initial dose and CIPN. RESULTS: Among 106 patients, 36 (34%) developed grade ≥2 CIPN during the first four cycles. More women experienced grade ≥2 CIPN (40%) than men (30%). Initial oxaliplatin dose, LBM, and sarcopenia were not significantly associated with grade ≥2 CIPN. No significant interactions were found between initial dose and LBM or sarcopenia. Notably, women had higher oxaliplatin dose intensity than men when normalized to LBM (5.5 vs 4.7 mg/kg), reflecting a larger discrepancy between their LBM and BSA. CONCLUSION: Although no significant associations were observed, sex-differences in LBM- adjusted dose intensity may suggest a potential role for LBM as a parameter in oxaliplatin dosing.

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