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

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/m(2) on day 1, plus capecitabine 1000 mg/m(2) 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.

• Authors: Toshihiko Doi, Narikazu Boku, Ken Kato, Yoshito Komatsu, Kensei Yamaguchi, Kei Muro, Yasuo Hamamoto, Atsushi Sato, Wasaburo Koizumi, Nobuyuki Mizunuma, Hiroya Takiuchi
• Journal: Japanese journal of clinical oncology (Jpn J Clin Oncol) Vol. 40 Issue 10 Pg. 913-20 (Oct 2010) ISSN: 1465-3621 [Electronic] England
• PMID: 20462981 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Organoplatinum Compounds
• Oxaliplatin
• Deoxycytidine
• Bevacizumab
• Capecitabine
• Fluorouracil

Topics

• Adult
• Aged
• Anorexia (chemically induced)
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Asian People
• Bevacizumab
• Capecitabine
• Colorectal Neoplasms (drug therapy, ethnology, pathology)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Fluorouracil (administration & dosage, adverse effects, analogs & derivatives)
• Humans
• Japan
• Male
• Middle Aged
• Nausea (chemically induced)
• Neoplasm Metastasis
• Organoplatinum Compounds (administration & dosage, adverse effects)
• Oxaliplatin
• Prospective Studies
• Sensation Disorders (chemically induced)
• Treatment Outcome