Optimal timing of chemotherapy in androgen independent prostate cancer

Purpose: To interpret available docetaxel clinical trial data in order to define optimal timing of the initiation of chemotherapy in androgen independent prostate cancer (AIPC). Materials and methods: Published literature on the natural history of nonmetastatic AIPC was reviewed. Phase III clinical trials using docetaxel-based therapy were analyzed as well as their associated quality of life (QOL) findings. Trials using docetaxel in earlier stage of the disease, as well those using novel agents were examined. Results: Based on one report, non-metastatic AIPC is relatively indolent, and there is currently no evidence that supports the use of chemotherapy in this disease subset. The results of TAX 327 and SWOG 9916 demonstrate that chemotherapy is indicated for metastatic AIPC. However, based on available data, more than one hormonal maneuver can be offered to patients before chemotherapy is initiated. Timing of docetaxel therapy can further be individualized based on risk, clinical status, and patients' values and preferences. Building on the success of docetaxel, several novel agents that target different pathways are being tested in combination with, or as an alternative to, docetaxel-based therapy in Phase III clinical trials. Conclusions: Currently, docetaxel therapy should be reserved for patients with metastatic AIPC who have progressed despite one or more hormonal therapies. In most patients, more than one hormonal treatment can be offered before chemotherapy is initiated. Studies that test the efficacy of chemotherapy early in the natural history of prostate cancer are under way or are planned.