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Profile of bevacizumab and its potential in the treatment of cervical cancer.

ABSTRACT: Blocking angiogenesis is an effective antitumor strategy proven in many disease sites. Anti-angiogenic therapies are fulfilling the promise of improved outcomes in cervical cancer as demonstrated in several recent trials. With its overall survival improvement in metastatic or recurrent cervical cancer, a frame shift in the management of these patients has occurred. The US Food and Drug Administration approval of bevacizumab in advanced cervical cancer has led to national guidelines, including the US National Comprehensive Cancer Network guidelines for cervical cancer, including systemic regimens containing bevacizumab as first line combination therapy. Future trials will build on this anti-angiogenesis backbone via targeting additional novel pathways and potentially leading to further improved outcomes in cervical cancer.

SUBMITTER: Fisher CM

PROVIDER: S-EPMC4657807 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Profile of bevacizumab and its potential in the treatment of cervical cancer.

Fisher Christine M CM Schefter Tracey E TE

OncoTargets and therapy 20151119

Blocking angiogenesis is an effective antitumor strategy proven in many disease sites. Anti-angiogenic therapies are fulfilling the promise of improved outcomes in cervical cancer as demonstrated in several recent trials. With its overall survival improvement in metastatic or recurrent cervical cancer, a frame shift in the management of these patients has occurred. The US Food and Drug Administration approval of bevacizumab in advanced cervical cancer has led to national guidelines, including th ...[more]

PMID: 26640382

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Project description:BackgroundVascular endothelial growth factor (VEGF) promotes angiogenesis, a mediator of disease progression in cervical cancer. Bevacizumab, a humanized anti-VEGF monoclonal antibody, has single-agent activity in previously treated, recurrent disease. Most patients in whom recurrent cervical cancer develops have previously received cisplatin with radiation therapy, which reduces the effectiveness of cisplatin at the time of recurrence. We evaluated the effectiveness of bevacizumab and nonplatinum combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer.MethodsUsing a 2-by-2 factorial design, we randomly assigned 452 patients to chemotherapy with or without bevacizumab at a dose of 15 mg per kilogram of body weight. Chemotherapy consisted of cisplatin at a dose of 50 mg per square meter of body-surface area, plus paclitaxel at a dose of 135 or 175 mg per square meter or topotecan at a dose of 0.75 mg per square meter on days 1 to 3, plus paclitaxel at a dose of 175 mg per square meter on day 1. Cycles were repeated every 21 days until disease progression, the development of unacceptable toxic effects, or a complete response was documented. The primary end point was overall survival; a reduction of 30% in the hazard ratio for death was considered clinically important.ResultsGroups were well balanced with respect to age, histologic findings, performance status, previous use or nonuse of a radiosensitizing platinum agent, and disease status. Topotecan-paclitaxel was not superior to cisplatin-paclitaxel (hazard ratio for death, 1.20). With the data for the two chemotherapy regimens combined, the addition of bevacizumab to chemotherapy was associated with increased overall survival (17.0 months vs. 13.3 months; hazard ratio for death, 0.71; 98% confidence interval, 0.54 to 0.95; P=0.004 in a one-sided test) and higher response rates (48% vs. 36%, P=0.008). Bevacizumab, as compared with chemotherapy alone, was associated with an increased incidence of hypertension of grade 2 or higher (25% vs. 2%), thromboembolic events of grade 3 or higher (8% vs. 1%), and gastrointestinal fistulas of grade 3 or higher (3% vs. 0%).ConclusionsThe addition of bevacizumab to combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer was associated with an improvement of 3.7 months in median overall survival. (Funded by the National Cancer Institute; GOG 240 ClinicalTrials.gov number, NCT00803062.).

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Profile of bevacizumab and its potential in the treatment of cervical cancer.

Publications

Profile of bevacizumab and its potential in the treatment of cervical cancer.

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