title: Vatalanib in malignant mesothelioma: a phase II trial by the Cancer and Leukemia Group B (CALGB 30107).
abstract: BACKGROUND
  The Cancer and Leukemia Group B (CALGB) conducted a multi-center phase II trial to evaluate the efficacy and safety of vatalanib in previously untreated patients with malignant mesothelioma and to evaluate potential biomarkers of disease response (CALGB 30107).
  
  
  METHODS
  Treatment consisted of vatalanib 1250 mg given orally once daily. CT scans were obtained at baseline and every 6 weeks thereafter. Baseline serum levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), thrombospondin-1 (TSP-1), and mesothelin were obtained. The primary endpoint was 3-month progression-free survival (PFS).
  
  
  RESULTS
  Forty-seven patients enrolled at 19 centers. The median age was 75 years, and the majority of patients (79%) had an ECOG performance status of 1. Tumors were classified as epithelial (77%), sarcomatoid (10%), or mixed (9%) histology. Toxicity was mild; the most common grade 3/4 adverse events were neutropenia (2%), nausea (15%), elevated alanine aminotransferase (11%), hypertension (2%), and gastrointestinal bleeding (2%). Partial responses were observed in 6% of patients and stable disease in 72% of patients. The 3-month PFS rate was 55% (95% CI: 40%, 68%). The median PFS was 4.1 months. Median overall survival was 10.0 months. There was no correlation between serum levels of VEGF, PDGF, TSP-1, or mesothelin and treatment response, PFS, or survival.
  
  
  CONCLUSIONS
  Vatalanib as a single agent with this dose and schedule does not warrant further study in this disease.
authors.affiliation: Department of Medicine, Division of Hematology Oncology, University of California, San Francisco, San Francisco, CA, USA. tjahan@medicine.ucsf.edu
authors.forename: Thierry
authors.initials: T
authors.lastname: Jahan
authors.forename: Lin
authors.initials: L
authors.lastname: Gu
authors.forename: Robert
authors.initials: R
authors.lastname: Kratzke
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Dudek
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Otterson
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.forename: Mark
authors.initials: M
authors.lastname: Green
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.forename: Hedy Lee
authors.initials: HL
authors.lastname: Kindler
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood; D006801:Humans; D008297:Male; D000090204:Mesothelin; D008654:Mesothelioma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D010793:Phthalazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010982:Platelet-Derived Growth Factor; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D019700:Thrombospondin 1 / Q000097:blood; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D010793:Phthalazines; D010982:Platelet-Derived Growth Factor; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; C404768:vatalanib; D000090204:Mesothelin