Phase I/II study on docetaxel, gemcitabine and prednisone in castrate refractory metastatic prostate cancer

Purpose We assessed the efficacy and toxicity of a fixed dose of docetaxel and prednisone, combined with escalating doses of gemcitabine (DGP). The primary endpoint was PSA response. Methods Fifteen patients were enrolled in the phase I and 50 patients entered the phase II. Patients were given DGP, maximum of eight courses, until progression or unacceptable toxicity. Docetaxel 75 mg/m² was administered intravenously day 1, gemcitabine was given day 1 and 8 in doses increasing from 600 to 1,000 mg/m² every third week. Patients had castrate refractory metastatic prostate cancer (CRMPC), adequate function of liver, kidney and bone marrow; ECOG performance status ≤2 and were chemotherapy-naïve. Results Median age was 64 range (49-77). Twenty-one (42%) were PS 0, 26 (52%) were PS 1 and 3 (6%) were PS 2. The median pre-treatment PSA was 448 (12-4.580). No dose limiting toxicity was observed even with the highest dose level in the phase I part of the study. In the phase II part, PSA response was observed in 37 (74%) patients. Twenty-four (48%) patients had measurable disease; 12 (50%) had partial remission, 5 (21%) had stable disease, 7 (29%) were not evaluable. Time to progression (TTP) was 7.9 months and overall survival (OS) was 13.9 months. Thirty-seven patients (74%) developed neutropenia, non-haematological toxicity was modest. Conclusions The PSA response rate was promising and the toxicity of DGP was manageable; however OS was comparable to results of treatment with single agent docetaxel.