Docetaxel and zoledronic acid in patients with metastatic hormone-refractory prostate cancer

To evaluate the safety and efficacy of combined docetaxel-zoledronic acid treatment in patients with metastatic hormone-refractory prostate cancer (HRPC), as bisphosphonates are reported have a synergistic antitumoral effect when combined with taxanes.

Between January 2001 and June 2003, 14 patients with HRPC were treated; their mean (range) age was 71 (57-86) years and mean prostate-specific antigen (PSA) level 202 (6-489) ng/mL. Five patients had had previous chemotherapy (cyclophosphamide in two, mitoxantrone-prednisolone in three). The response criteria were the Karnofsky performance status, a positive response in mean daily analgesic consumption (defined as a decrease by more than half), decreased serum PSA (by more than half) at 8 weeks, blood transfusion, bone scan at 6 months, skeletal-related events and survival.

Patients received a mean (range) of 7.3 (6-10) cycles of therapy; there was no reported drug-related toxicity and all patients stayed at home for their treatment. Only three patients required a blood transfusion and no bone fractures were reported. At 2 months, six patients requiring analgesic drugs decreased their consumption by more than half (anti-inflammatory, paracetamol, narcotics) and eight had a reduction in PSA by more than half; of these eight with a PSA response at 2 months, six had biochemical progression with a mean delay of 6.2 (3-11) months. At 6 months, five patients had disease progression on bone scan. Nine patients had chemo-naïve hormone-refractory prostate cancer; three had biochemical progression at 2 months and two of these had progression on their bone scan. Two patients died at 7 and 15 months of follow-up; the mean follow-up was 10.2 (6-15) months. Using Kaplan-Meier plots, biochemical progression-free survivals were five of 14 at 6 months and two of 14 at 12 months; overall survival was 12 of 14 at 6 and 12 months.

Docetaxel-zoledronic acid therapy is safe and decreased the serum PSA by more than half at 2 months in more than half the patients. Prospective randomized trials are needed to assess this new approach.