Phase I/II study of capecitabine plus oxaliplatin (XELOX) plus bevacizumab as first-line therapy in Japanese patients with metastatic colorectal cancer

Toshihiko Doi, Narikazu Boku, Ken Kato, Yoshito Komatsu, Kensei Yamaguchi, Kei Muro, Yasuo Hamamoto, Atsushi Sato, Wasaburo Koizumi, Nobuyuki Mizunuma, Hiroya Takiuchi

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Objective: The addition of bevacizumab to fluoropyrimidine-based combination chemotherapy as first-line therapy for metastatic colorectal cancer results in clinically significant improvements in patient outcome. However, clinical trials have been conducted primarily in Caucasian patients with only a small proportion of Asian patients. This Phase I/II study was designed to evaluate the efficacy and safety of XELOX (capecitabine plus oxaliplatin) plus bevacizumab in Japanese patients with metastatic colorectal cancer. Methods: Patients with previously untreated, measurable metastatic colorectal cancer received bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 on day 1, plus capecitabine 1000 mg/m2 twice daily on days 1-14, every 3 weeks. A three-step design evaluated in: step 1, initial safety of XELOX in six patients; step 2, initial safety of XELOX plus bevacizumab in six patients; and step 3, efficacy and safety in a further 48 patients. The primary study endpoints were safety and response rate. Results: No dose-limiting toxicity occurred during Steps 1 and 2. Fifty-eight patients were enrolled in Steps 2 and 3 and received XELOX plus bevacizumab. In the 57 patients assessed for response, the overall response rate was 72% (95% confidence interval, 58.5-83.0). Median progression-free survival was 11.0 months (95% confidence interval, 9.6-12.5) and median overall survival was 27.4 months (95% confidence interval, 22.0-not calculated). Eight patients (14%) underwent surgery with curative intent. The most common grade 3/4 adverse events were neurosensory toxicity (17%) and neutropenia (16%). Conclusions: XELOX plus bevacizumab is effective and has a manageable tolerability profile when given to Japanese patients with metastatic colorectal cancer.

Original languageEnglish
Article numberhyq069
Pages (from-to)913-920
Number of pages8
JournalJapanese Journal of Clinical Oncology
Volume40
Issue number10
DOIs
Publication statusPublished - 2010 May 12
Externally publishedYes

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oxaliplatin
Colorectal Neoplasms
Safety
Therapeutics
Confidence Intervals
XELOX
Capecitabine
Bevacizumab

Keywords

  • Bevacizumab
  • Colorectal cancer
  • Japanese
  • Xelox

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Radiology Nuclear Medicine and imaging

Cite this

Phase I/II study of capecitabine plus oxaliplatin (XELOX) plus bevacizumab as first-line therapy in Japanese patients with metastatic colorectal cancer. / Doi, Toshihiko; Boku, Narikazu; Kato, Ken; Komatsu, Yoshito; Yamaguchi, Kensei; Muro, Kei; Hamamoto, Yasuo; Sato, Atsushi; Koizumi, Wasaburo; Mizunuma, Nobuyuki; Takiuchi, Hiroya.

In: Japanese Journal of Clinical Oncology, Vol. 40, No. 10, hyq069, 12.05.2010, p. 913-920.

Research output: Contribution to journalArticle

Doi, T, Boku, N, Kato, K, Komatsu, Y, Yamaguchi, K, Muro, K, Hamamoto, Y, Sato, A, Koizumi, W, Mizunuma, N & Takiuchi, H 2010, 'Phase I/II study of capecitabine plus oxaliplatin (XELOX) plus bevacizumab as first-line therapy in Japanese patients with metastatic colorectal cancer', Japanese Journal of Clinical Oncology, vol. 40, no. 10, hyq069, pp. 913-920. https://doi.org/10.1093/jjco/hyq069
Doi, Toshihiko ; Boku, Narikazu ; Kato, Ken ; Komatsu, Yoshito ; Yamaguchi, Kensei ; Muro, Kei ; Hamamoto, Yasuo ; Sato, Atsushi ; Koizumi, Wasaburo ; Mizunuma, Nobuyuki ; Takiuchi, Hiroya. / Phase I/II study of capecitabine plus oxaliplatin (XELOX) plus bevacizumab as first-line therapy in Japanese patients with metastatic colorectal cancer. In: Japanese Journal of Clinical Oncology. 2010 ; Vol. 40, No. 10. pp. 913-920.
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abstract = "Objective: The addition of bevacizumab to fluoropyrimidine-based combination chemotherapy as first-line therapy for metastatic colorectal cancer results in clinically significant improvements in patient outcome. However, clinical trials have been conducted primarily in Caucasian patients with only a small proportion of Asian patients. This Phase I/II study was designed to evaluate the efficacy and safety of XELOX (capecitabine plus oxaliplatin) plus bevacizumab in Japanese patients with metastatic colorectal cancer. Methods: Patients with previously untreated, measurable metastatic colorectal cancer received bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 on day 1, plus capecitabine 1000 mg/m2 twice daily on days 1-14, every 3 weeks. A three-step design evaluated in: step 1, initial safety of XELOX in six patients; step 2, initial safety of XELOX plus bevacizumab in six patients; and step 3, efficacy and safety in a further 48 patients. The primary study endpoints were safety and response rate. Results: No dose-limiting toxicity occurred during Steps 1 and 2. Fifty-eight patients were enrolled in Steps 2 and 3 and received XELOX plus bevacizumab. In the 57 patients assessed for response, the overall response rate was 72{\%} (95{\%} confidence interval, 58.5-83.0). Median progression-free survival was 11.0 months (95{\%} confidence interval, 9.6-12.5) and median overall survival was 27.4 months (95{\%} confidence interval, 22.0-not calculated). Eight patients (14{\%}) underwent surgery with curative intent. The most common grade 3/4 adverse events were neurosensory toxicity (17{\%}) and neutropenia (16{\%}). Conclusions: XELOX plus bevacizumab is effective and has a manageable tolerability profile when given to Japanese patients with metastatic colorectal cancer.",
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AU - Boku, Narikazu

AU - Kato, Ken

AU - Komatsu, Yoshito

AU - Yamaguchi, Kensei

AU - Muro, Kei

AU - Hamamoto, Yasuo

AU - Sato, Atsushi

AU - Koizumi, Wasaburo

AU - Mizunuma, Nobuyuki

AU - Takiuchi, Hiroya

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