A phase I/II trial of 13-cis retinoic acid, alpha interferon, docetaxel, and estramustine (R.I.T.E.) for the treatment of hormone refractory prostate cancer (HRPC).

Abstract : Advanced prostate cancer is only temporarily controlled with androgen ablation therapy. In order to overcome tumor resistance, we developed a epithelial cell line model to dissect out important mechanisms of resistance such as mutations in p53 and bcl-2 overexpression. In an attempt to sensitize these cells to paclitaxel (TAX), we found that 13-cis retinoic acid and alpha interferon (CRA/IFN) was capable of overcoming bcl-2 mediated resistance and reduced the expression of bcl-2 in human prostate cancer cells. We hypothesized that drugs, which could overcome bcl-2 mediated resistance, would improve chemotherapy response or duration of response in the clinic. We then translated these results to the clinic in a series of clinical trials. Recently, our phase II study with CRA/IFN/TAX was acceped as a National trial and is ongoing in the Eastern Cooperative Oncolo%y Group. Given recet studies demonstrating that the combination of estramustine and docetaxes (ET) has increased response against HRPC in the clinic, but limited median duration of response, and our studies of CRA/IFN in the laboratory and clinic, we hypothesized that CRA/IFN will improve the response rate, or duration of response, of ET in patients with HRPC. We will treat patients with HRPC with R.I.T. E. therapy in a phase I and II trial.