JOIN trial: treatment outcome and recovery status of peripheral sensory neuropathy during a 3-year follow-up in patients receiving modified FOLFOX6 as adjuvant treatment for stage II/III colon cancer

Takayuki Yoshino,Akinori Takagane,Hideyuki Ishida,Yoshinori Munemoto,Yoshihiko Maehara,Dai Manaka,Keiji Inoue,Hiroshi Ishikawa,Tetsuo Touyama,Katsunori Shinozaki,Yutaka Ogata,Takanori Matsui,Masahito Kotaka,Junichi Hasegawa,Kiyoshi Ishigure,Koji Oba,Atsushi Ohtsu,Junichi Sakamoto,Koichi Goto

doi:10.1007/s00280-019-03957-5

Abstract

PurposeAdjuvant FOLFOX therapy is an established standard-of-care for resected colon cancer. Peripheral sensory neuropathy (PSN) is regarded as the major toxicity issue related to FOLFOX therapy. There have been a few reports on the recovery status from PSN thereafter. JOIN trial investigated the tolerability and efficacy of adjuvant modified FOLFOX6 (mFOLFOX6) in Japanese patients with stage II/III colon cancer.MethodsTwelve cycles of mFOLFOX6 were given to patients with stage II/III curatively resected colon cancer. Treatment outcomes, including disease-free survival (DFS), relapse-free survival (RFS), overall survival (OS), and recovery status of PSN during 3-year follow-up, were investigated.ResultsOf the 882 patients enrolled from 2010 to 2012, 864 were eligible for the efficacy analyses. Three-year DFS, RFS, and OS were favorable in 92.1, 92.8, and 97.4% of stage II patients; 76.4, 77.9, and 93.8% of stage IIIA/B; and 61.6, 62.7, and 85.9% of stage IIIC, respectively. The cumulative incidence of PSN during treatment was 47.8% in grade 1 (G1), 30.3% in G2, and 5.8% in G3. For those with G3 PSN during treatment, there was gradual recovery in 1.1% of patients at 12 months after enrollment, 0.5% at 24 months, and 0.2% at 36 months. However, G1 or G2 residual PSN after 3 years was observed in 21.0% (18.7%, G1; 2.3%, G2).ConclusionsAdjuvant mFOLFOX6 therapy was effective and well tolerated in patients with stage II/III colon cancer. Most patients recovered from G3 PSN related to oxaliplatin, but approximately 20% of patients had G1 or G2 PSN at 3-year follow-up.

Highlights

Six months of adjuvant oxaliplatin-based 5-fluorouracil (5-FU), leucovorin and oxaliplatin (FOLFOX) chemotherapy following surgery is the standard care for patients with stage III colon cancer as well as for patients with high-risk
FOLFOX4 has frequently been substituted by the modified FOLFOX6 regimen in the adjuvant setting [7, 8], which is easier to administer, and mFOLFOX6 has been shown to be tolerable in the adjuvant treatment of Japanese
The JOIN trial is a single-arm, multicenter, large-scale clinical trial across Japan to confirm the tolerability of adjuvant mFOLFOX6 in patients with curatively resected stage II/III colon cancer (UMIN ID: UMIN000004443)

Summary

Introduction

Six months of adjuvant oxaliplatin-based 5-fluorouracil (5-FU), leucovorin and oxaliplatin (FOLFOX) chemotherapy following surgery is the standard care for patients with stage III colon cancer as well as for patients with high-risk. FOLFOX4 regimen has proven efficacy in the adjuvant treatment of resected stage II and stage III colon cancers, as demonstrated by the pivotal MOSAIC [4, 5] and MASCOT [6] trials conducted in Western and Asian patient populations, respectively. In the adjuvant US NSABP C-08 trial [7] and Japanese JOIN trial [9] in which patients received the mFOLFOX6 regimen, the incidences of grade ≥ 3 PSN at the end of the studies were 14.4% and 5.8%, respectively. We report the treatment outcomes including diseasefree survival (DFS), relapse-free survival (RFS), overall survival (OS), and recovery rate from PSN during a 3-year follow-up

Methods

Results

Conclusion