Background The International Duration Evaluation of Adjuvant chemotherapy project investigated whether a shorter duration of oxaliplatin-based adjuvant chemotherapy was as effective as 6 months of identical chemotherapy for resected stage III colon cancer. As part of this project, we report safety data from the Japanese ACHIEVE study (JFMC47-1202-C3).
Patients and methods ACHIEVE was an open-label, multicentre trial randomising patients with stage III colon cancer to receive 3 m or 6 m of mFOLFOX6/CAPOX after surgery. Choice of regimen was declared before randomisation by a site investigator.
Results Between August 2012 and June 2014, 1313 patients were enrolled and, of those, 1277 were analysed for the safety analysis, with 635 in arm 6 (mFOLFOX6, n=158; CAPOX, n=477) and 642 in arm 3 (mFOLFOX6, n=161; CAPOX, n=481). Grade 3 or worse peripheral sensory neuropathy (PSN) developed in 5%/0.6% of patients receiving mFOLFOX6 in arm 6/3 (p=0.019) and 6%/1% of those receiving CAPOX in arm 6/3 (p<0.001). Similarly, grade 2 or worse PSN developed in 36%/11% of patients receiving mFOLFOX6 in arm 6/3 (p<0.001) and 37%/14% of those receiving CAPOX in arm 6/3 (p<0.001). An association between baseline creatinine clearance (CCr) and adverse events (AEs) was found that patients with CAPOX were significantly more likely to develop AEs ≥grade 3 when they had a CCr ≤50 (OR 1.67; p=0.048).
Conclusions We confirmed in the Japanese population that the shorter duration of adjuvant chemotherapy resulted in a significant reduction of PSN. In patients with CAPOX, renal function was significantly related to severe AEs.
Trial registration number UMIN000008543, Results.
- colon cancer
- adjuvant oxaliplatin
- treatment duration
- creatinine clearance
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Contributors Principal Investigators: MM, AO. Co-principal investigator and IDEA adjustment representative: TYa. Protocol coordinator: TYo. Research management investigators: TM, TYa. Person in charge of statistical analysis: TYo. Manuscript writing: all authors. Final approval of manuscript: all authors.
Funding This study was conducted by the Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC), a non-commercial organisation for investigator-initiated cancer trials, and funded by Yakult Honsha Co., Ltd.
Disclaimer Yakult Honsha had no role in design, collection, analysis or interpretation of the data, and writing the report.
Competing interests MK has received honoraria from Chugai Pharmaceutical, Takeda Pharmaceutical, Yakult Honsha, Taiho Pharmaceutical, Merck Serono. TYa has received honoraria from Chugai Pharmaceutical, Taiho Pharmaceutical, Takeda Pharmaceutical, Boehringer Ingelheim and research funding from Takeda Pharmaceutical. TYo has received honoraria from GlaxoSmithKline, Nippon Boehringer Ingelheim and research funding from Chugai Pharmaceutical, Taiho Pharmaceutical, Eli Lilly. MN has received honoraria from Merck, Takeda Pharmaceutical, Chugai Pharmaceutical, Yakult Honsha, Taiho Pharmaceutical, Eli Lilly and consulting fees from Merck, Bayer. TK has Speakers Bureau from Chugai Pharmaceutical, Takeda Pharmaceutical, Eli Lilly, Taiho Pharmaceutical. MG has received honoraria from Taiho Pharmaceutical, Chugai Pharmaceutical, Yakult Honsha, Ono Pharmaceutical, Takeda Pharmaceutical, Daiichi Sankyo, Nippon Kayaku, Eli Lilly. YM has Speakers Bureau from Chugai Pharmaceutical, Yakult Honsha and research funding from Chugai Pharmaceutical, Yakult Honsha, Kyowa Hakko Kirin. AO has received research funding from Bristol-Myers Squibb.
Patient consent Obtained.
Ethics approval National Cancer Center Hospital East, Chiba, Japan.
Provenance and peer review Not commissioned; internally peer reviewed.
Data sharing statement Our manuscript does not include additional unpublished data.
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