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Investigational New Drugs

, Volume 34, Issue 4, pp 468–473 | Cite as

Phase 1 study on S-1 and oxaliplatin therapy as an adjuvant after hepatectomy for colorectal liver metastases

  • Michiro Takahashi
  • Kiyoshi HasegawaEmail author
  • Masaru Oba
  • Akio Saiura
  • Junichi Arita
  • Yoshihiro Sakamoto
  • Eiji Shinozaki
  • Nobuyuki Mizunuma
  • Yutaka Matsuyama
  • Norihiro KokudoEmail author
PHASE I STUDIES

Summary

Summary 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/m2 and 100 mg/m2, respectively (level 1). We scheduled in the protocol a dose change of S-1 and oxaliplatin to level 2 (S-1: 80 mg/m2 and oxaliplatin: 130 mg/m2) or level 0 (S-1: 65 mg/m2 and oxaliplatin: 100 mg/m2) 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/m2 of S-1 and 130 mg/m2 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.

Keywords

Adjuvant therapy Colorectal liver metastases S-1 Oxaliplatin 

Notes

Compliance with ethical standards

Conflict of interest

Michiro Takahashi: No conflict of interest.

Kiyoshi Hasegawa: No conflict of interest.

Masaru Oba: No conflict of interest.

Akio Saiura: No conflict of interest.

Junichi Arita: No conflict of interest.

Yoshihiro Sakamoto: No conflict of interest.

Eiji Shinozaki: Honoraria- Takeda, Brystol Myers Squibb Japan, Taiho Pharmaceutical, Chugai Pharma, Ono Pharmaceutical.

Nobuyuki Mizunuma: No conflict of interest.

Yutaka Matsuyama: No conflict of interest.

Norihiro Kokudo: Honoraria- Taiho Pharmaceutical.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Michiro Takahashi
    • 1
    • 2
  • Kiyoshi Hasegawa
    • 1
    Email author
  • Masaru Oba
    • 1
  • Akio Saiura
    • 2
  • Junichi Arita
    • 1
    • 2
  • Yoshihiro Sakamoto
    • 1
  • Eiji Shinozaki
    • 3
  • Nobuyuki Mizunuma
    • 3
  • Yutaka Matsuyama
    • 4
  • Norihiro Kokudo
    • 1
    Email author
  1. 1.Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of MedicineUniversity of TokyoTokyoJapan
  2. 2.Department of Gastrointestinal SurgeryCancer Institute Hospital of the Japanese Foundation for Cancer ResearchTokyoJapan
  3. 3.Department of GastroenterologyCancer Institute Hospital of the Japanese Foundation for Cancer ResearchTokyoJapan
  4. 4.Department of BiostaticsUniversity of TokyoTokyoJapan

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