Estramustine phosphate and other cytotoxic drugs in the treatment of poor prognostic advanced prostate cancer

Hormonal treatment is effective for only a limited time in primary treatment of advanced prostate cancer, because of the development of hormone-resistant cells. It is unknown whether these cells were present in small numbers from the beginning or developed later by mutation of hormone-sensitive cells. Cytotoxic therapy has, up to now, mainly been used as second-line treatment when virtually all cells are hormone-resistant. Because 20% of all advanced prostate cancers do not respond to hormonal treatment even when given as primary therapy, hormone-resistant cells may have been present from the beginning. Trials using a combined hormonal and cytotoxic treatment as primary therapy would, therefore, be interesting. However, there is a lack of active compounds that do not show major toxicity. Estramustine phosphate (EMP) may be an exception. It is unusual because it combines hormonal and cytotoxic effects. Second-line treatment with chemotherapy has led to subjective improvement over a very short period of time only. EMP may be of benefit to patients who have had previous radiotherapy as it does not suppress the bone marrow. Although primary treatment of advanced prostate cancer with a combination of hormone and chemotherapy does not lead to a cure, it may extend time to progression, particularly in patients with poor prognostic factors at the onset. In future phase III studies, the role of prognostic factors must be further classified in order to obtain meaningful results.