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Cancer Chemotherapy and Pharmacology

, Volume 75, Issue 3, pp 587–594 | Cite as

A dose-escalation study of oxaliplatin/capecitabine/irinotecan (XELOXIRI) and bevacizumab as a first-line therapy for patients with metastatic colorectal cancer

  • Yasushi Sato
  • Hiroyuki Ohnuma
  • Masahiro Hirakawa
  • Minoru Takahashi
  • Takahiro Osuga
  • Yutaka Okagawa
  • Kazuyuki Murase
  • Kohichi Takada
  • Yutaka Kawano
  • Satoshi Iyama
  • Tsuyoshi Hayashi
  • Tsutomu Sato
  • Koji Miyanishi
  • Rishu Takimoto
  • Masayoshi Kobune
  • Kenji Okita
  • Toru Mizuguchi
  • Tomohisa Furuhata
  • Koichi Hirata
  • Junji KatoEmail author
Original Article

Abstract

Purpose

The aim of this study was to determine the recommended dose (RD) of a triweekly capecitabine, oxaliplatin, irinotecan, and bevacizumab (XELOXIRI/bevacizumab) regimen that was easier to administer than FOLFOXIRI/bevacizumab, using capecitabine instead of 5-fuorouracil (5-FU), in patients with metastatic colorectal cancer (mCRC).

Methods

Patients received oxaliplatin (100 mg/m2, day 1), capecitabine (1,700 mg/m2 per day from day 2 to 15), irinotecan (100, 120, 150 mg/m2 for dose levels 1, 2, 3, day 1), and bevacizumab (7.5 mg/kg, day 1), repeated every 3 weeks. Dose-limiting toxicities (DLTs) were assessed in the first two cycles to determine the maximum tolerated dose (MTD).

Results

Twelve patients received a median of 6.5 cycles of therapy (range 2–12). The DLT was grade 4 neutropenia, observed in one of six patients at dose level 2. The MTD was not reached at dose level 3. Therefore, the RD of irinotecan was defined as 150 mg/m2. The most common grade ≥3 toxicities were neutropenia (41 %), anemia (17 %), diarrhea (8 %), and febrile neutropenia (8 %). The response rate and median progression-free survival were 83 % and 15 months, respectively.

Conclusions

XELOXIRI/bevacizumab is a feasible regimen for patients with mCRC, neutropenia was the DLT, and the RD of irinotecan is 150 mg/m2. The response rate observed is very promising and warrants further investigation.

Keywords

Bevacizumab Capecitabine Colorectal cancer Irinotecan Oxaliplatin 

Notes

Conflict of interest

The authors have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Yasushi Sato
    • 1
  • Hiroyuki Ohnuma
    • 1
  • Masahiro Hirakawa
    • 1
  • Minoru Takahashi
    • 2
  • Takahiro Osuga
    • 1
  • Yutaka Okagawa
    • 1
  • Kazuyuki Murase
    • 1
  • Kohichi Takada
    • 1
  • Yutaka Kawano
    • 1
  • Satoshi Iyama
    • 1
  • Tsuyoshi Hayashi
    • 1
  • Tsutomu Sato
    • 1
  • Koji Miyanishi
    • 1
  • Rishu Takimoto
    • 1
  • Masayoshi Kobune
    • 1
  • Kenji Okita
    • 3
  • Toru Mizuguchi
    • 3
  • Tomohisa Furuhata
    • 3
  • Koichi Hirata
    • 3
  • Junji Kato
    • 1
    Email author
  1. 1.Department of Medical Oncology and HematologySapporo Medical University School of MedicineSapporoJapan
  2. 2.Division of GastroenterologySapporo Kyoritsu Gorinbashi HospitalSapporoJapan
  3. 3.Department of Surgery, Surgical Oncology and ScienceSapporo Medical University School of MedicineSapporoJapan

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