Treatment outcome and recovery from peripheral sensory neuropathy during a 3-year follow-up in patients receiving modified FOLFOX6 as adjuvant treatment for stage II/III colon cancer (JFMC41-1001-C2: JOIN Trial).

Abstract

703 Background: The JOIN Trial investigated safety and efficacy of modified FOLFOX6 (mFOLFOX6) in Japanese patients (pts) with stage II/III colon cancer. In the initial safety report, incidence of ≥ grade 3 (G3) peripheral sensory neuropathy (PSN) was 5.8% during treatment. Methods: Twelve cycles of mFOLFOX6 were given to pts with the following criteria: stage II/III curatively resected colon cancer; ECOG Performance Status (PS) of 0–1; age, ≥ 20 years; and adequate organ function. We report the treatment outcome results, including disease-free survival (DFS), relapse-free survival (RFS), overall survival (OS), and recovery from PSN during 3-year follow-up. Results: From November 2010 to March 2012, 882 pts were enrolled. In the efficacy group (N = 864; median follow-up, 3 years), pt characteristics were as follows: median age, 64 years; male, 53.8%; PS 0, 93.8%; stage II/IIIA/IIIB/IIIC (TNM), 18.5/7.3/52.5/21.6%; and lymph nodes examined, < 12/ > 12/unknown: 17.2/82.5/0.2%, respectively. Three-year DFS, RFS, and OS were 76.1, 77.3, and 92.7%, respectively. Favorable 3-year DFS, RFS, and OS were 92.1, 92.8, and 97.4% in stage II patients; 76.4, 77.9, and 93.8% in stage IIIA/B; and 61.6, 62.7, and 85.9% in stage IIIC, respectively. The main recurrent sites were liver (7.6%), lung (7.3%), and lymph nodes (5.2%). In multivariate Cox regression analysis, tumor histology, venous invasion, and lymph node metastatic ratio were statistically significant prognostic factors for DFS, RFS, and OS. Cumulative incidence of PSN during treatment was 47.8% in G1, 30.3% in G2, and 5.8% in G3. For those with G3 PSN during treatment, there was gradual recovery in 1.1% at 12 months after enrollment, 0.5% at 24 months, and 0.2% at 36 months. However, G1 and G2 residual PSN after 3 years was observed in 21.0% of pts (18.7%, G1; 2.3%, G2). Conclusions: Efficacy and safety of adjuvant mFOLFOX6 in pts with stage II/III colon cancer can be confirmed. Most pts successfully recovered from G3 PSN related to oxaliplatin, but G1 and G2 PSN was irreversible in one-fifth of pts at the 3-year follow-up. Clinical trial information: UMIN000004443.