Estramustine in combination with vinblastine and mitomycin-C for patients with progressive androgen independent adenocarcinoma of the prostate

A phase II trial was performed to assess the antitumor activity and toxicity of estramustine in combination with vinblastine and mitomycin-C in 46 consecutive patients with androgen independent prostate cancer. All patients presented with disease progression following castrate serum testosterone levels and were treated for six consecutive weeks with three daily 140 mg doses of oral estramustine, vinblastine at 5 mg/m2 weekly by intravenous bolus and mitomycin-C at 15 mg/m₂ every six weeks by intravenous bolus. Prostate specific antigen levels decreased by greater than 50% from baseline in 16 (41%; 95% CI 25-58%) and normalized in 11 (28%; 95% CI 14- 45%) of 39 evaluable patients. Patients who demonstrated a greater than 50% reduction in PSA had a longer delay in time to disease progression. Non- hematologic toxicity was mild, predominately gastrointestinal. Hematologic toxicity was apparent in five patients with Grade III granulocytopenia and in 21 patients with Grade IV granulocytopenia of 43 evaluable patients for toxicity. Three patients were admitted to the hospital for neutropenic fever. Eight patients had Grade III thrombocytopenia, four patients had Grade IV thrombocytopenia, no bleeding occurred. Estramustine in combination with vinblastine and mitomycin-C is an active regimen. The non-hematologic toxicity was tolerable, while the hematologic toxicity required individual dosage reduction. The combination and the clinical significance of the decline in the PSA warrants further investigation.