title: A pilot study of antiangiogenic therapy with bevacizumab and thalidomide in patients with metastatic renal cell carcinoma.
abstract: The use of antiangiogenic agents represents a promising strategy for the treatment of patients with metastatic renal cell carcinoma. Objective responses to single-agent thalidomide have been described, and a randomized study showed that bevacizumab (a neutralizing antibody against vascular endothelial growth factor) delayed time to progression of metastatic renal cancer. A pilot study combining these two agents was performed. Sequential cohorts of 10 and 12 patients (crossing over from placebo therapy in the aforementioned randomized bevacizuamab trial) were treated with low-dose bevacizumab alone or bevacizumab plus the maximum tolerated dose of thalidomide as determined by intrapatient escalation. Toxicity, objective responses, and time to progression were the endpoints of this study. Patients tolerated thalidomide and bevacizumab well, with more than 50% of patients escalating to at least 500 mg/d thalidomide. Grades 1 and 2 sensory neuropathy limited thalidomide dose escalation in 3 of 12 patients. The incidence of grades 3 and 4 toxicity was not different between patients treated with bevacizumab alone versus bevacizumab plus thalidomide. There were no objective responses and no difference in progression-free survival between the groups (2.4 months for bevacizumab alone, 3.0 months for bevacizumab plus thalidomide). Combination antiangiogenic therapy with bevacizumab plus thalidomide in patients with renal cell carcinoma is associated with similar toxicity and progression-free survival compared with bevacizumab alone. This study illustrates a clinical trial design for rapidly testing the feasibility and safety of combining antiangiogenic agents, an approach that will be necessary for rapidly evaluating the many potential combinations of antiangiogenic agents.
authors.affiliation: Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Dina M
authors.initials: DM
authors.lastname: Elaraj
authors.forename: Donald E
authors.initials: DE
authors.lastname: White
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Leah
authors.initials: L
authors.lastname: Haworth
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: James C
authors.initials: JC
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010865:Pilot Projects; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D013792:Thalidomide