title: Preplanned safety analysis of the JFMC37-0801 trial: a randomized phase III study of six months versus twelve months of capecitabine as adjuvant chemotherapy for stage III colon cancer.
abstract: BACKGROUND
  Six months of adjuvant chemotherapy is regarded as the standard of care for patients with stage III colon cancer. However, whether longer treatment can improve prognosis has not been fully investigated. We conducted a phase III study comparing 6 and 12 months of adjuvant capecitabine chemotherapy for stage III colon cancer, and report here the results of our preplanned safety analysis.
  
  
  METHODS
  Patients aged 20-79 years with curatively resected stage III colon cancer were randomly assigned to receive 8 cycles (6 months) or 16 cycles (12 months) of capecitabine (2500 mg/m2/day on days 1-14 of each 21-day cycle). Treatment exposure and adverse events (AEs) were evaluated.
  
  
  RESULTS
  A total of 1304 patients (642 and 636 in the 6-month and 12-month groups, respectively) were analyzed. The most common AE was hand-foot syndrome (HFS). HFS, leukocytopenia, neutropenia, and hyperbilirubinemia (any grade) occurred more frequently in the 12-month group than in the 6-month group. HFS was the only grade ≥3 AE to have a significantly higher incidence in the 12-month group (23 vs 17%, p = 0.011). The completion rate for 8 cycles was 72% in both groups, while that for 16 cycles was 46% in the 12-month group. HFS was the most common AE requiring dose reduction and treatment discontinuation.
  
  
  CONCLUSIONS
  Twelve months of adjuvant capecitabine demonstrated a higher cumulative incidence of HFS compared to the standard 6-month treatment period, while toxicities after 12 months of capecitabine were clinically acceptable.
  
  
  BACKGROUND
  UMIN-CTR, UMIN000001367.
authors.affiliation: Department of Gastroenterological Surgery, Yamagata Prefectural Central Hospital, 1800 Aoyagi, Yamagata-shi, Yamagata, 990-2214, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suto
authors.affiliation: Department of Translational Oncology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Ishiguro
authors.affiliation: Graduate School of Engineering, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo, 125-8585, Japan.
authors.forename: Chikuma
authors.initials: C
authors.lastname: Hamada
authors.affiliation: Department of Surgery, Gifu Prefectural General Medical Center, 4-6-1 Noishiki, Gifu-shi, Gifu, 500-8717, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kunieda
authors.affiliation: Department of Surgery, Nikko Memorial Hospital, 1-5-13 Shintomi-cho, Muroran-shi, Hokkaido, 051-8501, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Masuko
authors.affiliation: Department of Surgery, National Hospital Organization Nagoya Medical Center, 4-1-1 Sannomaru, Naka-ku, Nagoya-shi, Aichi, 460-0001, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe-shi, Saitama, 350-8550, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ishida
authors.affiliation: Department of Surgery, Kanazawa Red Cross Hospital, 2-251 Mimma, Kanazawa-shi, Ishikawa, 921-8162, Japan.
authors.forename: Genichi
authors.initials: G
authors.lastname: Nishimura
authors.affiliation: Department of Surgery, Otaru Ekisaikai Hospital, 1-10-17 Ironai, Otaru-shi, Hokkaido, 047-0031, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Surgery, Aomori Prefectural Central Hospital, 2-1-1 Higashitsukurimichi, Aomori-shi, Aomori, 030-8553, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Morita
authors.affiliation: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube-shi, Yamaguchi, 755-8505, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Hazama
authors.affiliation: Department of Lower Gastrointestinal Surgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake-shi, Aichi, 470-1192, Japan.
authors.forename: Koutarou
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Cancer Center, Aichi Medical University, 1-1 Yazakokarimata, Nagakute-shi, Aichi, 480-1195, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Mishima
authors.affiliation: Department of Surgery, Saiseikai Yokohama Southern Hospital, 3-2-10 Konandai, Konan-ku, Yokohama-shi, Kanagawa, 234-8503, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ike
authors.affiliation: Department of Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara-shi, Kanagawa, 259-1193, Japan.
authors.forename: Sotaro
authors.initials: S
authors.lastname: Sadahiro
authors.affiliation: Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
authors.affiliation: The Second Department of Surgery, Hiroshima University School of Medicine, 7-33 Motomachi, Naka-ku, Hiroshima-shi, Hiroshima, 730-8518, Japan.
authors.forename: Masazumi
authors.initials: M
authors.lastname: Okajima
authors.affiliation: Japanese Foundation for Multidisciplinary Treatment of Cancer, 1-28-6 Kameido, Koto-ku, Tokyo, 136-0071, Japan.
authors.forename: Shigetoyo
authors.initials: S
authors.lastname: Saji
authors.affiliation: Japanese Foundation for Multidisciplinary Treatment of Cancer, 1-28-6 Kameido, Koto-ku, Tokyo, 136-0071, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.affiliation: Division of Lower Gastrointestinal Surgery, Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya-shi, Hyogo, 663-8501, Japan. ntomita@hyo-med.ac.jp.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Tomita
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D060831:Hand-Foot Syndrome / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000069287:Capecitabine
keywords: Adjuvant chemotherapy; Adverse events; Capecitabine; Colon cancer; Hand-foot syndrome; Treatment duration