Etoposide in the treatment of hormone-refractory advanced carcinoma of the prostate.

The leading cause of cancer in males in the United States, prostate cancer accounts for 22% of all new cancers, with 132,000 new cases projected to be diagnosed in 1992. While localized prostate cancer can be cured, up to two thirds of patients present with advanced disease. Androgen deprivation remains the mainstay of treatment for advanced prostate carcinoma. Recurrent disease, however, is invariably refractory to further hormone manipulations. The development of hormone-resistant tumor cells may be explained either by a multi-clones theory, by mutation of previously sensitive tumor cell clones, or, most likely, by both mechanisms. Thus, vigorous efforts are needed to develop nonendocrine treatment approaches. Such efforts have been complicated by the difficulty of assessing therapeutic response in patients with prostate cancer, because the typical metastatic bone lesions seen in these patients are difficult to measure accurately and patients seldom have disease in the lung, lymph nodes, or soft tissue. A variety of single chemotherapeutic agents have been tested against recurrent disease, with widely divergent response rates achieved. Trials of chemohormonal therapy have likewise proved disappointing to date. Preliminary results from an ongoing trial of oral etoposide in patients with recurrent prostate cancer are discussed.