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.

We previously showed that the incidenceof oxaliplatin-induced peripheral neurotoxicity (OIPN) is higher for oxaliplatin doses >3.09 mg per kg of lean body mass (LBM).

我们之前的研究表明，奥沙利铂诱导的外周神经毒性（OIPN）的发生率对于每公斤瘦体质量（LBM）超过3.09毫克的奥沙利铂剂量更高。

This proof-of-concept, multicenter, randomized trial assessed whether LBM-based oxaliplatin dose adjustment reduces OIPN (ClinicalTrials.gov identifier: NCT03255434).

这项概念验证的多中心随机试验评估了基于瘦体质量（LBM）的奥沙利铂剂量调整是否能减少奥沙利铂诱导的周围神经病变（OIPN）的发生。（临床试验注册号：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/m2, arm 1).

在适合接受辅助性左旋亚叶酸、氟尿嘧啶和奥沙利铂化疗的III期结肠癌切除患者中，没有瘦体质量（LBM）减少的患者接受了基于体表面积（BSA）的奥沙利铂剂量（每平方米85毫克，第1组）。

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).

具有减少的瘦体质量（LBM）的患者被随机分配（1:1），以接受基于体表面积（BSA）的（第2组）或基于LBM的奥沙利铂剂量（每公斤LBM 3.09毫克，第3组）。

The primary end point was the percentage of patients without grade ≥2 OIPN in the first six cycles.

主要终点是前六个周期内没有2级或更高级别OIPN的患者百分比。

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).

共有33名、64名和63名患者分别进入第1组、第2组和第3组（中位年龄为63岁；男性占52.5%；89.3%为东部肿瘤协作组0级；57.5%为pT3期；60.6%为pN1期）。

The primary end point was achieved by 67.2% of patients in arm 3 versus 42.1% in arm 2 (P = .01).

第3组的67.2%患者达到了主要终点，而第2组为42.1%（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.

在第三组中报告了更长的2级及以上OIPN无进展生存期（风险比[HR]，0.53 [95%置信区间，0.34至0.84]；P = .01），更长的2级及以上OIPN发作时间（P = .006），在没有2级及以上OIPN的情况下接受更高累积剂量的奥沙利铂（P = .044），以及更少的奥沙利铂剂量减少（P < .001）。

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).

在第2组和第3组中，无复发生存期（HR，1.05 [95% CI, 0.54 to 2.06]）和总生存期（OS；HR，1.20 [95% CI, 0.36 to 3.92]）相似（中位随访时间为38.6个月）。

Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 scores were better in arm 3.

在第三组中，化疗诱导的周围神经病变生活质量问卷20的评分更好。

Conclusions

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.

在III期结肠癌辅助治疗中，基于瘦体质量的奥沙利铂剂量显著减少OIPN并改善生活质量，而不影响无复发生存期和总生存期。