The case for early chemotherapy for the treatment of metastatic disease

Several important questions are raised by the data from Southwest Oncology Group 99-16 and TAX 327. What is the optimal timing of chemotherapy for metastatic hormone refractory prostate cancer? Should asymptomatic patients be treated? Is there a theoretical survival advantage for treatment for hormone sensitive prostate cancer? We reviewed arguments for the early use of docetaxel in the hormone sensitive and hormone naïve disease states.

Androgen independent prostate cancer was traditionally viewed as a chemoresistant disease. At best palliation of bone pain but not improved survival could be achieved with the combination of mitoxantrone and prednisone. Median survival rates for chemotherapy in this disease state were reported to be between 10 and 12 months. Phase II studies administering docetaxel weekly or every 3 weeks as a single agent or in combination with estramustine demonstrated median survival rates of 14 to 23 months, which appeared to be an improvement over standard therapy. Consequently the 2 randomized trials, Southwest Oncology Group 99-16 and TAX 327, were designed to confirm the preliminary observations of improved survival with docetaxel based therapy.

TAX 327 and Southwest Oncology Group 99-16 treated asymptomatic as well as symptomatic patients. Thus, in contrast with mitoxantrone/prednisone, which was approved in symptomatic men with hormone refractory prostate cancer, the exact timing of the initiation of chemotherapy in docetaxel treated patients is still the subject of debate.

Studies should be performed to investigate the optimal timing of chemotherapy as well as sequencing with androgen ablation in patients at high risk for progression and death from metastatic prostate cancer. Prognostic factors for death that have been identified in patients with androgen independent prostate cancer are hemoglobin, alkaline phosphatase, visceral disease and performance status.