Introduction: 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.
Bibliographical noteFunding Information:
Dana-Farber Cancer Institute, Boston, MA – Harold J. Burstein, M.D., Ph.D., supported by CA32291 .
Georgetown University Medical Center, Washington, DC – Minetta C. Liu, M.D., supported by CA77597 .
University of Minnesota, Minneapolis, MN – Bruce A. Peterson, M.D., supported by CA16450 .
Nevada Cancer Research Foundation CCOP, Las Vegas, NV – John A. Ellerton, M.D., supported by CA35421 .
The research for CALGB 30107 was supported, in part, by grants from the National Cancer Institute ( CA31946 ) to the Cancer and Leukemia Group B (Monica M. Bertagnolli, M.D., Chair) and to the CALGB Statistical Center (Daniel J. Sargent, Ph.D., CA33601 ). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.
University of Chicago, Chicago, IL – Hedy L. Kindler M.D., supported by CA41287 .
Duke University Medical Center, Durham, NC – Jeffrey Crawford, M.D., supported by CA47577 .
Christiana Care Health Services, Inc., CCOP, Wilmington, DE – Stephen Grubbs, M.D., supported by CA45418 .
- Clinical trial phase II
- Molecular targeted therapy
- VEGF Receptor