Impact of Lean Body Mass–Based Oxaliplatin Dose Calculation on Neurotoxicity in Adjuvant Treatment of Stage III Colon Cancer: Results of the Phase II Randomized LEANOX Trial

Abstract

PURPOSE Oxaliplatin-based adjuvant chemotherapy is used for stage III colon cancer, but may induce disabling neurotoxicity. We previously showed that the incidence of oxaliplatin-induced peripheral neurotoxicity (OIPN) is higher for oxaliplatin doses >3.09 mg per kg of lean body mass (LBM). This proof-of-concept, multicenter, randomized trial assessed whether LBM-based oxaliplatin dose adjustment reduces OIPN (ClinicalTrials.gov identifier: NCT03255434 ). METHODS Among the patients with resected stage III colon cancer eligible for adjuvant leucovorin, fluorouracil, and oxaliplatin chemotherapy, those without LBM reduction received body surface area (BSA)–based oxaliplatin doses (85 mg/m 2 , arm 1). Patients with reduced LBM were randomly assigned (1:1) to receive BSA-based (arm 2) or LBM-based oxaliplatin doses (3.09 mg/kg LBM, arm 3). The primary end point was the percentage of patients without grade ≥2 OIPN in the first six cycles. RESULTS In all, 33, 64, and 63 patients were enrolled in arms 1, 2, and 3, respectively (median age, 63 years; 52.5% of men; 89.3% Eastern Cooperative Oncology Group 0; 57.5% pT3; 60.6% pN1). The primary end point was achieved by 67.2% of patients in arm 3 versus 42.1% in arm 2 ( P = .01). Longer grade ≥2 OIPN-free survival (hazard ratio [HR], 0.53 [95% CI, 0.34 to 0.84]; P = .01), longer time to grade ≥2 OIPN onset ( P = .006), higher cumulative oxaliplatin doses without grade ≥2 OIPN ( P = .044), and fewer oxaliplatin dose reductions ( P < .001) were reported in arm 3. Relapse-free survival (HR, 1.05 [95% CI, 0.54 to 2.06]) and overall survival (OS; HR, 1.20 [95% CI, 0.36 to 3.92]) were similar in arms 2 and 3 (median follow-up of 38.6 months). Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 scores were better in arm 3. CONCLUSION In adjuvant settings for stage III colon cancer, using an LBM-based oxaliplatin dose significantly reduces OIPN and improves quality of life without affecting relapse-free survival and OS.