Phase II study of pemetrexed and carboplatin plus bevacizumab as first-line therapy in malignant pleural mesothelioma

• Published in: British journal of cancer Vol. 109; no. 3; pp. 552 - 558
• Main Authors: Ceresoli, G L, Zucali, P A, Mencoboni, M, Botta, M, Grossi, F, Cortinovis, D, Zilembo, N, Ripa, C, Tiseo, M, Favaretto, A G, Soto-Parra, H, De Vincenzo, F, Bruzzone, A, Lorenzi, E, Gianoncelli, L, Ercoli, B, Giordano, L, Santoro, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.08.2013; Nature Publishing Group
• Subjects: 631/154/109/1941; 692/699/67/1059/99; 692/699/67/1641; Adult; Aged; Angiogenesis; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cancer therapies; Carboplatin - administration & dosage; Carboplatin - adverse effects; Chemotherapy; Clinical Study; Disease-Free Survival; Drug Resistance; Effectiveness; Epidemiology; Female; Glutamates - administration & dosage; Glutamates - adverse effects; Guanine - administration & dosage; Guanine - adverse effects; Guanine - analogs & derivatives; Hematology; Humans; Kaplan-Meier Estimate; Male; Medical prognosis; Medical research; Medical sciences; Mesothelioma; Mesothelioma - blood; Mesothelioma - drug therapy; Middle Aged; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Oncology; Patients; Pemetrexed; Pleural Neoplasms - blood; Pleural Neoplasms - drug therapy; Pneumology; Treatment Outcome; Tumors; Tumors of the respiratory system and mediastinum; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - blood; Italy; bevacizumab; mesothelioma; chemotherapy; Antineoplastic agent; Respiratory disease; Monoclonal antibody; Malignant tumor; Pemetrexed; Bevacizumab; First line treatment; Antifolate; Immunomodulator; Chemotherapy; Treatment; Cancerology; Vascular endothelium growth factor; Phase II trial; Carboplatin; Pleural disease; Malignant pleural mesothelioma; Antiangiogenic agent; Cancer; Platinum II Complexes
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2013.368

Background: The aim of this open label phase II study (NCT00407459) was to assess the activity of the vascular endothelial growth factor (VEGF) inhibitor bevacizumab combined with pemetrexed and carboplatin in patients with previously untreated, unresectable malignant pleural mesothelioma (MPM). Methods: Eligible patients received pemetrexed 500 mg m −2 , carboplatin area under the plasma concentration–time curve (AUC) 5 mg ml −1 per minute and bevacizumab 15 mg kg −1 , administered intravenously every 21 days for six cycles, followed by maintenance bevacizumab. The primary end point of the study was progression-free survival (PFS). A 50% improvement in median PFS in comparison with standard pemetrexed/platinum combinations (from 6 to 9 months) was postulated. Results: Seventy-six patients were evaluable for analysis. A partial response was achieved in 26 cases (34.2%, 95% CI 23.7–46.0%). Forty-four (57.9%, 95% CI 46.0–69.1%) had stable disease. Median PFS and overall survival were 6.9 and 15.3 months, respectively. Haematological and non-haematological toxicities were generally mild; however, some severe adverse events were reported, including grade 3–4 fatigue in 8% and bowel perforation in 4% of patients. Three toxic deaths occurred. Conclusion: The primary end point of the trial was not reached. However, due to the limitation of a non-randomised phase II design, further data are needed before drawing any definite conclusion on the role of bevacizumab in MPM.