title: Phase II study of pemetrexed and carboplatin plus bevacizumab as first-line therapy in malignant pleural mesothelioma.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Oncology, Cliniche Humanitas Gavazzeni, Bergamo, Italy. giovanni_luca.ceresoli@gavazzeni.it
authors.forename: G L
authors.initials: GL
authors.lastname: Ceresoli
authors.forename: P A
authors.initials: PA
authors.lastname: Zucali
authors.forename: M
authors.initials: M
authors.lastname: Mencoboni
authors.forename: M
authors.initials: M
authors.lastname: Botta
authors.forename: F
authors.initials: F
authors.lastname: Grossi
authors.forename: D
authors.initials: D
authors.lastname: Cortinovis
authors.forename: N
authors.initials: N
authors.lastname: Zilembo
authors.forename: C
authors.initials: C
authors.lastname: Ripa
authors.forename: M
authors.initials: M
authors.lastname: Tiseo
authors.forename: A G
authors.initials: AG
authors.lastname: Favaretto
authors.forename: H
authors.initials: H
authors.lastname: Soto-Parra
authors.forename: F
authors.initials: F
authors.lastname: De Vincenzo
authors.forename: A
authors.initials: A
authors.lastname: Bruzzone
authors.forename: E
authors.initials: E
authors.lastname: Lorenzi
authors.forename: L
authors.initials: L
authors.lastname: Gianoncelli
authors.forename: B
authors.initials: B
authors.lastname: Ercoli
authors.forename: L
authors.initials: L
authors.lastname: Giordano
authors.forename: A
authors.initials: A
authors.lastname: Santoro
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008654:Mesothelioma / Q000097:blood / Q000188:drug therapy*; D008875:Middle Aged; D000068437:Pemetrexed; D010997:Pleural Neoplasms / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005971:Glutamates; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068437:Pemetrexed; D000068258:Bevacizumab; D006147:Guanine; D016190:Carboplatin