Vinblastine and Estramustine Phosphate in Metastatic Renal Cell Carcinoma: A Phase II Trial of the Fox Chase Network

BACKGROUND. It is well known that metastatic renal cell carcinoma (RCC) exhibits constitutive resistance to chemotherapeutic agents. Antimicrotubule agents such as vinblastine are associated with low but reproducible response rates (approximately 12%) in patients with RCC. Estramustine has been shown to potentiate the antimicrotubule effects of vinblastine. The authors sought to increase the activity of vinblastine in RCC through the addition of estramustine. METHODS. Twenty-one patients with metastatic RCC not previously treated with chemotherapy received oral estramustine phosphate, 600 mg/m ², on Days 1, 2, and 3 weekly for 6 weeks, and intravenous vinblastine, 4 mg/m² on Day 2 weekly for 6 weeks, repeated every 8 weeks. Twenty-one patients received 31 cycles of therapy. RESULTS. Two patients experienced Grade 3 and 4 hematologic toxicity, and three patients had Grade 3 nonhematologic toxicity consisting of neurologic toxicity, hepatic toxicity, or angioneurotic edema. One patient had a partial response with decreased liver metastases for 48 weeks; 9 patients had stable disease, for a median duration of 14 weeks (range, 11-31 weeks); and 11 patients demonstrated disease progression. The median overall time to progression was 8 weeks and the median overall survival period was 24 weeks. CONCLUSIONS. Although well tolerated, the combination of oral estramustine phosphate with vinblastine administered on this schedule had minimal activity in patients with metastatic RCC.