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Safety data from the phase III Japanese ACHIEVE trial: part of an international, prospective, planned pooled analysis of six phase III trials comparing 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer
  1. Masahito Kotaka1,
  2. Takeharu Yamanaka2,
  3. Takayuki Yoshino3,
  4. Dai Manaka4,
  5. Tetsuya Eto5,
  6. Junichi Hasegawa6,
  7. Akinori Takagane7,
  8. Masato Nakamura8,
  9. Takeshi Kato9,
  10. Yoshinori Munemoto10,
  11. Fumitaka Nakamura11,
  12. Hiroyuki Bando12,
  13. Hiroki Taniguchi13,
  14. Makio Gamoh14,
  15. Manabu Shiozawa15,
  16. Shigetoyo Saji16,
  17. Yoshihiko Maehara17,
  18. Tsunekazu Mizushima18,
  19. Atsushi Ohtsu3,
  20. Masaki Mori18
  1. 1 Gastrointestinal Cancer Center, Sano Hospital, Hyogo, Japan
  2. 2 Department of Biostatistics, Yokohama City University School of Medicine, Kanagawa, Japan
  3. 3 Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan
  4. 4 Department of Surgery, Gastrointestinal Center, Kyoto Katsura Hospital, Kyoto, Japan
  5. 5 Department of Gastroenterology, Tsuchiura Kyodo General Hospital, Ibaraki, Japan
  6. 6 Department of Surgery, Osaka Rosai Hospital, Osaka, Japan
  7. 7 Department of Surgery, Hakodate Goryoukaku Hospital, Hokkaido, Japan
  8. 8 Aizawa Comprehensive Cancer Center, Aizawa Hospital, Nagano, Japan
  9. 9 Department of Surgery, Kansai Rosai Hospital, Hyogo, Japan
  10. 10 Department of Surgery, Fukui-ken Saiseikai Hospital, Fukui, Japan
  11. 11 Department of Surgery, Teine Keijinkai Hospital, Hokkaido, Japan
  12. 12 Gastroenterological Surgery, Ishikawa Prefectural Central Hospital, Ishikawa, Japan
  13. 13 Department of Surgery, Kyoto Second Red Cross Hospital, Kyoto, Japan
  14. 14 Department of Medical Oncology, Osaki Citizen Hospital, Miyagi, Japan
  15. 15 Gastrointestinal Surgery, Kanagawa Cancer Center, Kanagawa, Japan
  16. 16 Japanese Foundation for Multidisciplinary Treatment of Cancer, Tokyo, Japan
  17. 17 Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
  18. 18 Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
  1. Correspondence to Dr Takayuki Yoshino; tyoshino{at}east.ncc.go.jp

Abstract

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
  • neuropathy
  • treatment duration
  • creatinine clearance

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Footnotes

  • 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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