A multicenter phase II study of cisplatin, pemetrexed, and bevacizumab in patients with advanced malignant mesothelioma

Jonathan E. Dowell, Frank R. Dunphy, Robert N. Taub, David E. Gerber, Likheng Ngov, Jingsheng Yan, Yang Xie, Hedy Lee Kindler

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Introduction: Malignant mesothelioma (MM) cells express the vascular endothelial growth factor (VEGF) receptor, and VEGF protein expression is detected in a majority of human mesothelioma biopsy specimens. Bevacizumab is a recombinant humanized monoclonal antibody that blocks the binding of VEGF to its receptor. We evaluated the addition of bevacizumab to cisplatin and pemetrexed as first-line treatment in patients with advanced, unresectable MM. Methods: Previously untreated MM patients with advanced, unresectable disease received cisplatin (75mg/m2), pemetrexed (500mg/m2), and bevacizumab (15mg/kg) intravenously every 21days for a maximum of 6cycles. Patients with responsive or stable disease received bevacizumab (15mg/kg) intravenously every 21days until progression or intolerance. The primary endpoint was progression-free survival rate at 6months. Results: 53 patients were enrolled at 4 centers; 52 were evaluable for this analysis. The progression-free survival rate at 6. months was 56% and the median progression-free survival was 6.9. months (95% confidence interval [CI], 5.3-7.8. months). The partial response rate was 40% and 35% of patients had stable disease. Median overall survival was 14.8. months (95% CI; 10.0-17.0. months). Grade 3/4 toxicities included neutropenia in 11%, hypertension in 6%, and venous thromboembolism in 13% of patients. Conclusion: This trial evaluating the addition of bevacizumab to cisplatin and pemetrexed in patients with previously untreated, advanced MM failed to meet the primary endpoint of a 33% improvement in the progression-free survival rate at 6. months compared with historical controls treated with cisplatin and pemetrexed alone.

Original languageEnglish (US)
Pages (from-to)567-571
Number of pages5
JournalLung Cancer
Volume77
Issue number3
DOIs
StatePublished - Sep 2012

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Pemetrexed
Cisplatin
Disease-Free Survival
Survival Rate
Vascular Endothelial Growth Factor A
Confidence Intervals
Antibodies, Monoclonal, Humanized
Vascular Endothelial Growth Factor Receptor
Mesothelioma
Venous Thromboembolism
Bevacizumab
Malignant Mesothelioma
Neutropenia
Hypertension
Biopsy

Keywords

  • Bevacizumab
  • Chemotherapy
  • Mesothelioma

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

A multicenter phase II study of cisplatin, pemetrexed, and bevacizumab in patients with advanced malignant mesothelioma. / Dowell, Jonathan E.; Dunphy, Frank R.; Taub, Robert N.; Gerber, David E.; Ngov, Likheng; Yan, Jingsheng; Xie, Yang; Kindler, Hedy Lee.

In: Lung Cancer, Vol. 77, No. 3, 09.2012, p. 567-571.

Research output: Contribution to journalArticle

Dowell, Jonathan E. ; Dunphy, Frank R. ; Taub, Robert N. ; Gerber, David E. ; Ngov, Likheng ; Yan, Jingsheng ; Xie, Yang ; Kindler, Hedy Lee. / A multicenter phase II study of cisplatin, pemetrexed, and bevacizumab in patients with advanced malignant mesothelioma. In: Lung Cancer. 2012 ; Vol. 77, No. 3. pp. 567-571.
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abstract = "Introduction: Malignant mesothelioma (MM) cells express the vascular endothelial growth factor (VEGF) receptor, and VEGF protein expression is detected in a majority of human mesothelioma biopsy specimens. Bevacizumab is a recombinant humanized monoclonal antibody that blocks the binding of VEGF to its receptor. We evaluated the addition of bevacizumab to cisplatin and pemetrexed as first-line treatment in patients with advanced, unresectable MM. Methods: Previously untreated MM patients with advanced, unresectable disease received cisplatin (75mg/m2), pemetrexed (500mg/m2), and bevacizumab (15mg/kg) intravenously every 21days for a maximum of 6cycles. Patients with responsive or stable disease received bevacizumab (15mg/kg) intravenously every 21days until progression or intolerance. The primary endpoint was progression-free survival rate at 6months. Results: 53 patients were enrolled at 4 centers; 52 were evaluable for this analysis. The progression-free survival rate at 6. months was 56{\%} and the median progression-free survival was 6.9. months (95{\%} confidence interval [CI], 5.3-7.8. months). The partial response rate was 40{\%} and 35{\%} of patients had stable disease. Median overall survival was 14.8. months (95{\%} CI; 10.0-17.0. months). Grade 3/4 toxicities included neutropenia in 11{\%}, hypertension in 6{\%}, and venous thromboembolism in 13{\%} of patients. Conclusion: This trial evaluating the addition of bevacizumab to cisplatin and pemetrexed in patients with previously untreated, advanced MM failed to meet the primary endpoint of a 33{\%} improvement in the progression-free survival rate at 6. months compared with historical controls treated with cisplatin and pemetrexed alone.",
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T1 - A multicenter phase II study of cisplatin, pemetrexed, and bevacizumab in patients with advanced malignant mesothelioma

AU - Dowell, Jonathan E.

AU - Dunphy, Frank R.

AU - Taub, Robert N.

AU - Gerber, David E.

AU - Ngov, Likheng

AU - Yan, Jingsheng

AU - Xie, Yang

AU - Kindler, Hedy Lee

PY - 2012/9

Y1 - 2012/9

N2 - Introduction: Malignant mesothelioma (MM) cells express the vascular endothelial growth factor (VEGF) receptor, and VEGF protein expression is detected in a majority of human mesothelioma biopsy specimens. Bevacizumab is a recombinant humanized monoclonal antibody that blocks the binding of VEGF to its receptor. We evaluated the addition of bevacizumab to cisplatin and pemetrexed as first-line treatment in patients with advanced, unresectable MM. Methods: Previously untreated MM patients with advanced, unresectable disease received cisplatin (75mg/m2), pemetrexed (500mg/m2), and bevacizumab (15mg/kg) intravenously every 21days for a maximum of 6cycles. Patients with responsive or stable disease received bevacizumab (15mg/kg) intravenously every 21days until progression or intolerance. The primary endpoint was progression-free survival rate at 6months. Results: 53 patients were enrolled at 4 centers; 52 were evaluable for this analysis. The progression-free survival rate at 6. months was 56% and the median progression-free survival was 6.9. months (95% confidence interval [CI], 5.3-7.8. months). The partial response rate was 40% and 35% of patients had stable disease. Median overall survival was 14.8. months (95% CI; 10.0-17.0. months). Grade 3/4 toxicities included neutropenia in 11%, hypertension in 6%, and venous thromboembolism in 13% of patients. Conclusion: This trial evaluating the addition of bevacizumab to cisplatin and pemetrexed in patients with previously untreated, advanced MM failed to meet the primary endpoint of a 33% improvement in the progression-free survival rate at 6. months compared with historical controls treated with cisplatin and pemetrexed alone.

AB - Introduction: Malignant mesothelioma (MM) cells express the vascular endothelial growth factor (VEGF) receptor, and VEGF protein expression is detected in a majority of human mesothelioma biopsy specimens. Bevacizumab is a recombinant humanized monoclonal antibody that blocks the binding of VEGF to its receptor. We evaluated the addition of bevacizumab to cisplatin and pemetrexed as first-line treatment in patients with advanced, unresectable MM. Methods: Previously untreated MM patients with advanced, unresectable disease received cisplatin (75mg/m2), pemetrexed (500mg/m2), and bevacizumab (15mg/kg) intravenously every 21days for a maximum of 6cycles. Patients with responsive or stable disease received bevacizumab (15mg/kg) intravenously every 21days until progression or intolerance. The primary endpoint was progression-free survival rate at 6months. Results: 53 patients were enrolled at 4 centers; 52 were evaluable for this analysis. The progression-free survival rate at 6. months was 56% and the median progression-free survival was 6.9. months (95% confidence interval [CI], 5.3-7.8. months). The partial response rate was 40% and 35% of patients had stable disease. Median overall survival was 14.8. months (95% CI; 10.0-17.0. months). Grade 3/4 toxicities included neutropenia in 11%, hypertension in 6%, and venous thromboembolism in 13% of patients. Conclusion: This trial evaluating the addition of bevacizumab to cisplatin and pemetrexed in patients with previously untreated, advanced MM failed to meet the primary endpoint of a 33% improvement in the progression-free survival rate at 6. months compared with historical controls treated with cisplatin and pemetrexed alone.

KW - Bevacizumab

KW - Chemotherapy

KW - Mesothelioma

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