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Bevacizumab in the therapy for refractory metastatic colorectal cancer.

ABSTRACT: Colorectal cancer is the second most common cause of cancer related deaths in the United States. Recent developments have led to prolonged survival with the use of sequential lines of chemotherapy agents. The addition of bevacizumab to active chemotherapy has further improved survival when used in the first and second lines of therapy for metastatic colorectal cancer. Evidence supporting the continued use of bevacizumab throughout lines of therapy is accumulating. Clinical trials are underway in which bevacizumab is continued beyond the first line of a chemotherapy and bevacizumab combination regimen. The mechanism by which colorectal cancer may become resistant to bevacizumab is poorly understood. Molecular and biochemical correlates which may identify bevacizumab resistance are an important component in the design of these clinical trials.

SUBMITTER: Mulcahy MF

PROVIDER: S-EPMC2727788 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

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Bevacizumab in the therapy for refractory metastatic colorectal cancer.

Mulcahy Mary F MF

Biologics : targets & therapy 20080301 1

Colorectal cancer is the second most common cause of cancer related deaths in the United States. Recent developments have led to prolonged survival with the use of sequential lines of chemotherapy agents. The addition of bevacizumab to active chemotherapy has further improved survival when used in the first and second lines of therapy for metastatic colorectal cancer. Evidence supporting the continued use of bevacizumab throughout lines of therapy is accumulating. Clinical trials are underway in ...[more]

PMID: 19707427

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Project description:AimThe use of bevacizumab in combination therapy is an emerging trend in metastatic colorectal cancer treatment. However, the clinical value of different combination types remains under debate. Thus, a meta-analysis of randomized controlled trials (RCTs) comparing bevacizumab-based combination therapy with monotherapy (therapy that uses one type of treatment, such as chemotherapy or surgery alone, to treat metastatic colorectal cancer) was performed, aiming to evaluate the safety and efficacy of bevacizumab-based combination therapy and to find a more beneficial combination.MethodsWe searched for clinical studies that evaluated bevacizumab-based combination therapy in metastatic colorectal cancer. We extracted data from these studies to evaluate the relative risk (RR) of overall response rate (ORR) and grade 3/4 treatment-related adverse events (AEs), HRs of overall survival (OS), and progression-free survival (PFS).ResultsEight RCTs were identified (n=3,424). Treatments included combinations of bevacizumab and oxaliplatin, fluorouracil, and leucovorin (FOLFOX4), combinations of bevacizumab and capecitabine and oxaliplatin, combinations of bevacizumab and fluorouracil/leucovorin, combinations of bevacizumab and irinotecan, fluorouracil, and leucovorin (IFL), and combinations of bevacizumab and capecitabine. Bevacizumab-based combination therapy showed higher ORR (RR: 1.40; 95% CI: 1.10–1.78; P=0.005), PFS (HR: 0.64; 95% CI: 0.55–0.73; P=0.000), and OS (HR: 0.82; 95% CI: 0.73–0.92; P=0.001) values than monotherapy. However, higher grade 3/4 treatment-related AEs (RR: 1.27; 95% CI: 1.15–1.41; P=0.000) were observed in combination therapy than in monotherapy.ConclusionThis meta-analysis showed that the addition of IFL to bevacizumab better benefits PFS and safety. Adding FOLFOX4 was associated with better ORR and OS. The efficacy and safety of an IFL–bevacizumab–FOLFOX4 combination should be given greater weight in future clinical trials, guidelines, and clinical practice.

Dataset Information

Bevacizumab in the therapy for refractory metastatic colorectal cancer.

Publications

Bevacizumab in the therapy for refractory metastatic colorectal cancer.

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