Lean Body Mass-Based Dose Adjustments Significantly Reduces the Rate of Oxaliplatin-Induced Peripheral Neurotoxicity in Colon Cancer

According to results from the phase 2 LEANOX trial, using lean body mass to adjust oxaliplatin dosage significantly reduced the rate of oxaliplatin-induced peripheral neurotoxicity compared to body surface area-based adjustments among patients with stage 3 colon cancer.

“Oxaliplatin-based chemotherapy often induces chronic peripheral neurotoxicity, significantly affecting clinical outcomes and quality of life,” stated Eric Assenat, MD, PhD, Montpellier Cancer Institute (ICM),  France, and coauthors. “Oxaliplatin dose is usually based on the patient's body surface area; however, it is not clear whether dose adjustments based on lean body mass could reduce oxaliplatin-induced peripheral neurotoxicity in patients with colon cancer.” 

In this multicenter, proof-of-concept trial, researchers enrolled 63 patients with resected stage 3 colon cancer eligible to undergo adjuvant leucovorin, fluorouracil, and oxaliplatin. Those who did not have lean body mass reduction were assigned to receive 85 mg/m² of oxaliplatin based on body surface area (n = 33). Patients with lean body mass reduction were randomized on a 1-to-1 basis to receive either body surface area-based (n = 64) or 3.09 mg/kg of lean body mass-based (n = 63) oxaliplatin. The primary end point was the rate of patients without grade ≥2 oxaliplatin-induced peripheral neurotoxicity. Key secondary end points included relapse-free survival (RFS) and overall survival (OS). 

At analysis, the rate of patients without grade ≥2 oxaliplatin-induced peripheral neurotoxicity was 42.1% in arm 2 and 67.2% in arm 3 (P = .01). Oxaliplatin-induced peripheral neurotoxicity-free survival rate was significantly greater in arm 2 compared to arm 3 (hazard ratio [HR] 0.53; 95% confidence interval [CI], 0.34 to 0.84; P = .01). Median time to oxaliplatin-induced peripheral neurotoxicity was 2.3 months in arm 2 and 5.7 months in arm 3 (P = .006). The median cumulative oxaliplatin dose delivered without reaching grade ≥2 oxaliplatin-induced peripheral neurotoxicity was 465.9 mg/m² in arm 2 and 18.54 mg/kg in arm 3 (P = .04). Patients in arm 3 underwent fewer dose reductions (P < .001). RFS and OS rates were similar between treatment arms.

“This randomized clinical trial demonstrated that individualized [lean body mass]-based chemotherapy dose calculation significantly reduces [oxaliplatin-induced peripheral neurotoxicity],” concluded Dr Assenat et al. 

“The practicality of this approach will depend on widespread adoption of radiology software tools that can provide reliable body composition measurements,” added Journal of Clinical Oncology associate editor Andrew Ko, MD, Helen Diller Family Comprehensive Cancer Center, San Francisco, California.

Source: 

Assenat E, Abdelghani MB, Gourgou S, et al. 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. J Clin Oncol. Published online: June 20, 2025. doi: 10.1200/JCO-24-02754