Patient-reported neurotoxicity with FULV versus FLOX in patients with stage II or III carcinoma of the colon: Results of NSABP Protocol C-07

Abstract

3564 Background: NSABP Phase III Protocol C-07 compared the efficacy of FULV versus FLOX in patients with stage II or III colon cancer. The definitive analysis revealed an increase in 3-year disease-free survival from 71.6% to 76.5% (HR=0.79, p=0.004) in favor of FLOX. The present study compares patient-reported neurotoxicity between the treatment groups. Methods: Patients were randomized to either FULV (5-FU, 500 mg/m2 iv bolus weekly x 6; LV, 500 mg/m2 iv weekly x 6, each 8-week cycle x 3) or FLOX (FULV with oxaliplatin 85 mg/m2 iv administered on weeks 1, 3 and 5 of each 8-week cycle x 3). A subset of patients (planned sample size 400) at select institutions completed the validated FACT/GOG Oxaliplatin-Specific Neurotoxicity Scale (NTX-12) at baseline, week 4 of cycle 2, and at 6, 12 and 18 months. Mean NTX-12 scores were compared between treatments at 18 months using a t-test and longitudinally with mixed effects modeling. Item responses were compared between treatments with logistic regression. Results: From February 2000 to July 2001, 395 patients with follow-up (206 FULV, 189 FLOX) were enrolled in the neurotoxicity study. They were comparable by disease stage and site, age, and sex to the 759 concurrently accrued C-07 patients not in the sub-study (data not shown). NTX-12 form submission rates were high (with a low of 77% at 12 months). Mean neurotoxicity was higher in the oxaliplatin arm throughout the period of study (p<0.0001) and remained higher at 18 months (p=0.009). During therapy, FLOX patients experienced significant increases in hand/foot neuropathy and overall weakness, and an improvement in hearing ( Table ). At 18 months, hand neurotoxicity resolved, but patients who received oxaliplatin experienced ringing in the ears and continued foot discomfort. Conclusions: This presentation provides the first public review of the severity and persistence of neurotoxicity associated with oxaliplatin in this study. [Table: see text] [Table: see text]