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

OBJECTIVE 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. PATIENTS AND METHODS 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. RESULTS 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. CONCLUSION 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.