Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: A randomized phase III study Journal Article
| Authors: | Saltz, L. B.; Clarke, S.; Díaz-Rubio, E.; Scheithauer, W.; Figer, A.; Wong, R.; Koski, S.; Lichinitser, M.; Yang, T. S.; Rivera, F.; Couture, F.; Sirzén, F.; Cassidy, J. |
| Article Title: | Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: A randomized phase III study |
| Abstract: | Purpose: To evaluate the efficacy and safety of bevacizumab when added to first-line oxaliplatin-based chemotherapy (either capecitabine plus oxaliplatin [XELOX] or fluorouracil/folinic acid plus oxaliplatin [FOLFOX-4]) in patients with metastatic colorectal cancer (MCRC). Patients and Methods: Patients with MCRC were randomly assigned, in a 2 x 2 factorial design, to XELOX versus FOLFOX-4, and then to bevacizumab versus placebo. The primary end point was progression-free survival (PFS). Results: A total of 1,401 patients were randomly assigned in this 2 x 2 analysis. Median progression-free survival (PFS) was 9.4 months in the bevacizumab group and 8.0 months in the placebo group (hazard ratio [HR], 0.83; 97.5% CI, 0.72 to 0.95; P = .0023). Median overall survival was 21.3 months in the bevacizumab group and 19.9 months in the placebo group (HR, 0.89; 97.5% CI, 0.76 to 1.03; P = .077). Response rates were similar in both arms. Analysis of treatment withdrawals showed that, despite protocol allowance of treatment continuation until disease progression, only 29% and 47% of bevacizumab and placebo recipients, respectively, were treated until progression. The toxicity profile of bevacizumab was consistent with that documented in previous trials. Conclusion: The addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved PFS in this first-line trial in patients with MCRC. Overall survival differences did not reach statistical significance, and response rate was not improved by the addition of bevacizumab. Treatment continuation until disease progression may be necessary in order to optimize the contribution of bevacizumab to therapy. © 2008 by American Society of Clinical Oncology. |
| Keywords: | controlled study; disease-free survival; middle aged; treatment failure; major clinical study; overall survival; clinical trial; disease course; fistula; bevacizumab; fluorouracil; placebo; diarrhea; drug efficacy; drug safety; drug withdrawal; hypertension; treatment planning; capecitabine; disease free survival; neurotoxicity; antineoplastic agent; colorectal cancer; metastasis; controlled clinical trial; multiple cycle treatment; bleeding; heart disease; randomized controlled trial; vomiting; antineoplastic combined chemotherapy protocols; abdominal abscess; drug administration schedule; combination chemotherapy; pathology; cetuximab; irinotecan; monoclonal antibody; colorectal neoplasms; antibodies, monoclonal; multicenter study; thromboembolism; colorectal tumor; folinic acid; neoplasm metastasis; drug derivative; phase 3 clinical trial; platinum complex; drug administration; oxaliplatin; hand foot syndrome; deoxycytidine; digestive system perforation; wound healing impairment; organoplatinum compounds; infusions, intravenous; gastrointestinal disease; leucovorin; proteinuria; intravenous drug administration; placebos; venous thromboembolism |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 26 |
| Issue: | 12 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2008-04-20 |
| Start Page: | 2013 |
| End Page: | 2019 |
| Language: | English |
| DOI: | 10.1200/jco.2007.14.9930 |
| PUBMED: | 18421054 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | This article has been republished at DOI: 10.1200/jco.22.02760 - "Cited By (since 1996): 500" - "Export Date: 17 November 2011" - "CODEN: JCOND" - "Source: Scopus" |
