BACKGROUND: Renal cell carcinoma (RCC) is characterized by increased expression of vascular endothelial growth factor and platelet-derived growth factor (PDGF)-beta, both of which contribute to its angiogenic phenotype. Interferon-alpha (IFN-alpha) improves survival in patients with metastatic RCC, perhaps partly because of its antiangiogenic properties. Imatinib mesylate inhibits PDGF-mediated signal transduction and might thus have antiangiogenic activity as well. PATIENTS AND METHODS: Patients with metastatic RCC were treated with IFN-alpha (9 million IU subcutaneously 3 times weekly) and oral imatinib mesylate (600 mg daily starting on day 8). Therapy was continuous, and response was evaluated at 8-week intervals using the Response Evaluation Criteria in Solid Tumors. Baseline plasma PDGF-AA, PDGF-AB, and PDGF-BB levels were obtained. RESULTS: Between January 2003 and January 2005, 17 patients were treated. One patient (6%) had a partial response, 4 (24%) had stable disease, 7 (41%) had progressive disease, and 5 (29%) were unevaluable because of early withdrawal secondary to toxicity. Median time to progression (TTP) using the Kaplan-Meier method was 8 weeks, and median overall survival was 17.8 months. Six patients (35%) withdrew from therapy because of toxicity, and 9 patients (53%) experienced > or = 1 grade 3/4 toxicity. Platelet-derived growth factor AA, AB, and BB plasma levels did not correlate with TTP or overall survival. CONCLUSION: Based on a response rate of only 6%, a median TTP of 2 months, and significant toxicities, further study of IFN-alpha in combination with imatinib mesylate is not recommended in patients with metastatic RCC.
BACKGROUND:Renal cell carcinoma (RCC) is characterized by increased expression of vascular endothelial growth factor and platelet-derived growth factor (PDGF)-beta, both of which contribute to its angiogenic phenotype. Interferon-alpha (IFN-alpha) improves survival in patients with metastatic RCC, perhaps partly because of its antiangiogenic properties. Imatinib mesylate inhibits PDGF-mediated signal transduction and might thus have antiangiogenic activity as well. PATIENTS AND METHODS: Patients with metastatic RCC were treated with IFN-alpha (9 million IU subcutaneously 3 times weekly) and oral imatinib mesylate (600 mg daily starting on day 8). Therapy was continuous, and response was evaluated at 8-week intervals using the Response Evaluation Criteria in Solid Tumors. Baseline plasma PDGF-AA, PDGF-AB, and PDGF-BB levels were obtained. RESULTS: Between January 2003 and January 2005, 17 patients were treated. One patient (6%) had a partial response, 4 (24%) had stable disease, 7 (41%) had progressive disease, and 5 (29%) were unevaluable because of early withdrawal secondary to toxicity. Median time to progression (TTP) using the Kaplan-Meier method was 8 weeks, and median overall survival was 17.8 months. Six patients (35%) withdrew from therapy because of toxicity, and 9 patients (53%) experienced > or = 1 grade 3/4 toxicity. Platelet-derived growth factor AA, AB, and BB plasma levels did not correlate with TTP or overall survival. CONCLUSION: Based on a response rate of only 6%, a median TTP of 2 months, and significant toxicities, further study of IFN-alpha in combination with imatinib mesylate is not recommended in patients with metastatic RCC.
Authors: Christopher W Ryan; Jacqueline Vuky; Joseph S Chan; Zunqiu Chen; Tomasz M Beer; Deirdre Nauman Journal: Invest New Drugs Date: 2009-12-10 Impact factor: 3.651