title: Phase 1 study on S-1 and oxaliplatin therapy as an adjuvant after hepatectomy for colorectal liver metastases.
abstract: of Background Data The effectiveness of adjuvant chemotherapy in patients with stage II/III colorectal cancer has been confirmed in various studies. However, no adjuvant chemotherapy for colorectal liver metastasis (CLM) classified to stage IV has been established. Objectives We conducted a phase 1 study of S-1 and oxaliplatin to determine the recommended dose (RD) in patients with CLM as adjuvant therapy in two institutes. Methods S-1 and oxaliplatin were administered from day 1 to day 14 of a 3-week cycle as a 2-h infusion every 3 weeks, respectively. The initial doses of S-1 and oxaliplatin were fixed to 80 mg/m(2) and 100 mg/m(2), respectively (level 1). We scheduled in the protocol a dose change of S-1 and oxaliplatin to level 2 (S-1: 80 mg/m(2) and oxaliplatin: 130 mg/m(2)) or level 0 (S-1: 65 mg/m(2) and oxaliplatin: 100 mg/m(2)) depending on the incidence of dose-limiting toxicity (DLT) at level 1 in six patients. Results Because DLT occurred in one among the initial six patients at level 1, the doses were increased to level 2 in the next six patients. At level 2, grade 3 leukopenia and neutropenia occurred in one (16.7 %) and two (33.3 %) patients, respectively, in the absence of non-hematological event. Because no DLT occurred at level 2, we suggest that the RD can be set to the level 2 dose. The median number of cycles delivered at RD was 8. The mean relative dose intensity of S-1 and oxaliplatin at RD was 0.90 and 0.63, respectively. Conclusion In a patient undergoing hepatectomy for CLM, 80 mg/m(2) of S-1 and 130 mg/m(2) of oxaliplatin are recommended as adjuvant therapy. A further study is required to confirm the efficacy and safety of this regimen on a larger scale.
authors.affiliation: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.|Department of Gastrointestinal Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Michiro
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. kihase-tky@umin.ac.jp.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Oba
authors.affiliation: Department of Gastrointestinal Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Saiura
authors.affiliation: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.|Department of Gastrointestinal Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Arita
authors.affiliation: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Shinozaki
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Mizunuma
authors.affiliation: Department of Biostatics, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Matsuyama
authors.affiliation: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. KOKUDO-2SU@h.u-tokyo.ac.jp.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kokudo
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004338:Drug Combinations; D005260:Female; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D005641:Tegafur / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid
keywords: Adjuvant therapy; Colorectal liver metastases; Oxaliplatin; S-1