Cytotoxic chemotherapy for advanced hormone-resistant prostate cancer

Advanced adenocarcinoma of the prostate after hormonal manipulation has been noted to be a relatively chemotherapeutic nonresponsive tumor. Earlier reviews have reported objective responses, that is, complete and partial remissions in 6.5% of 3184 patients, and the current review examines the efficacy of new agents.

The current review consists of 26 new drug trials culled from papers and abstracts published between 1987-1991.

Results of these 26 drug trials found a similar trend, 8.7% (95% confidence interval, 6.4-9.0%), indicating that hormone-resistant adenocarcinoma of the prostate still fails to respond to most cytotoxic agents. The most interesting of the new therapeutic agents is the combination of vinblastine plus estramustine. Only six agents had an objective response rate greater than 10%, such as vinblastine by continuous infusion, trimetrexate, mitoguazone, and estramustine. The recent introduction of radioactive-labeled monoclonal antibodies is intriguing and these will undoubtably be used as carriers for radiotherapeutic and cytotoxic compounds.

Although multidrug resistance may explain the marginal efficacy of cytotoxic drugs, methods to overcome such resistance and, more importantly, new classes of agents must be developed. In addition, reliable disease markers must be found for osseous and visceral metastases to avoid the prevailing confusion in evaluating more precisely the destruction of prostate cancer cells.