Beyond Platinum for Metastatic and Recurrent Carcinoma of the Cervix

Tewari, Krishnansu S.; Monk, Bradley J.

doi:10.1159/000232385

Cited by 12 publications

(4 citation statements)

References 9 publications

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“…Previously, chemotherapy using cisplatin plus paclitaxel in these settings had been palliative, with rapid clinical deterioration, worsened quality of life (QoL), and median overall survival (OS) ranging from 7-12 months (3,4). Importantly, many patients with recurrent disease have been pre-irradiated with limited bone marrow reserves, and may be platinum-resistant as a consequence of prior platinum exposure with radiotherapy and subsequent acquired drug resistance (5,6). In addition, many are medically infirm due to renal failure and malnutrition.…”

Section: Introductionmentioning

confidence: 99%

Prospective Validation of Pooled Prognostic Factors in Women with Advanced Cervical Cancer Treated with Chemotherapy with/without Bevacizumab: NRG Oncology/GOG Study

Tewari

Sill

Monk

et al. 2015

Clinical Cancer Research

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Purpose In the randomized phase III trial, Gynecologic Oncology Group protocol 240, the incorporation of bevacizumab with chemotherapy significantly increased overall survival (OS) in women with advanced cervical cancer. A major objective of GOG-240 was to prospectively analyze previously identified pooled clinical prognostic factors known as the Moore criteria. Experimental Design Potential negative factors included black race, performance status 1, pelvic disease, prior cisplatin, and progression-free interval <365 days. Risk categories included low-risk (0-1 factor); intermediate-risk (2-3 factors); high-risk (4-5 factors). Each test of association was conducted at the 5% level of significance. Logistic regression and survival analysis was used to determine whether factors were prognostic or could be used to guide therapy. Results For the entire population (n=452), high-risk patients had significantly worse OS (p<0.0001). The hazard ratios of death for treating with topotecan in low-risk, mid-risk, and high-risk subsets are 1.18 (95% CI 0.63-2.24), 1.11 (95% CI 0.82-1.5), and 0.84 (95% CI 0.50-1.42), respectively. The hazard ratios of death for treating with bevacizumab in low-risk, mid-risk, and high-risk subsets are 0.96 (95% CI 0.51-1.83; p=0.9087), 0.673 (95% CI 0.5-0.91; p=0.0094), and 0.536 (95% CI 0.32-0.905; p=0.0196), respectively. Conclusions This is the first prospectively validated scoring system in cervical cancer. The Moore criteria have real world clinical applicability. Toxicity concerns may justify omission of bevacizumab in some low-risk patients where survival benefit is small. The benefit to receiving bevacizumab appears to be greatest in the moderate- and high-risk subgroups (5.8 month increase in median OS).

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Section: Introductionmentioning

confidence: 99%

Prospective Validation of Pooled Prognostic Factors in Women with Advanced Cervical Cancer Treated with Chemotherapy with/without Bevacizumab: NRG Oncology/GOG Study

Tewari

Sill

Monk

et al. 2015

Clinical Cancer Research

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“…Assuming an absence of interaction between experimental agents, we used a 2-by-2 factorial design to investigate the effect of anti-VEGF therapy (bevacizumab) and a regimen of nonplatinum combination chemotherapy (topotecan–paclitaxel). 25 The study was based on the intention-to-treat principle. Patients were prospectively stratified according to GOG performance status, prior use or nonuse of radiosensi tizing platinum, and disease status (recurrence or persistence of disease vs. advanced primary disease).…”

Section: Methodsmentioning

confidence: 99%

Improved Survival with Bevacizumab in Advanced Cervical Cancer

et al. 2014

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Background-Vascular 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.

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“…Assuming an absence of interaction between experimental agents, we used a 2-by-2 factorial design to investigate the effect of anti-VEGF therapy (bevacizumab) and a regimen of nonplatinum combination chemotherapy (topotecan-paclitaxel). 25 The study was based on the intentionto-treat principle. Patients were prospectively stratified according to GOG performance status, prior use or nonuse of radiosensi tizing platinum, and disease status (recurrence or persistence of disease vs. advanced primary disease).…”

Section: Discussionmentioning

confidence: 99%