A phase II trial of 13-cis retinoic acid, interferon, docetaxel, and estramustine (RITE) for the treatment of hormone refractory prostate cancer (HRPC)

Abstract

15542 Background: Efficacy of chemotherapy for the treatment of HRPC is limited secondary to the development of multiple mechanisms of resistance. In our prior studies, we demonstrated the safety and activity of docetaxel (T) 40 mg/m2 given with 13-cis retinoic acid (R), interferon alpha (I) and estramustine (E), along with a decrease in the expression of the anti-apoptotic protein Bcl-2. To test whether this regimen had clinical activity in HRPC, we conducted a phase II trial with the combination of these drugs. Methods: Eligible patients (pts) received 13-cis retinoic acid 1 mg/kg on days 1 to 4, interferon alfa 6 million units/m2 on days 1 to 4, estramustine 280 mg three times a day on days 1 to 5, and docetaxel 40 mg/m2 on day 2, all repeated every 21 days. Pts had peripheral blood mononuclear cells (PBMCs) obtained prior to therapy and on days 2 through 4 of the first cycle to assess the effect of therapy on the expression of Bcl-2. Results: Nineteen of 20 registered pts (mean age 66) have been treated in this trial. The median pre-treatment PSA was 33.3 ng/mL. A PSA decrease was seen in 13/19 pts (68%) with a mean decrease of 50.3%. A PSA decrease ≥ 50% was seen in 7/19 pts (37%), with an average PSA decrease of 70.4% in these pts. One patient had an objective response (partial remission). The median time to progression (TTP) was 16.3 weeks (range: 3.1 - 132.6 weeks). Three pts remain on study with a median TTP of 25.1 weeks (range: 6.1 - 132.6 weeks). Grade 3 toxicities included 2 pts with hypophosphatemia, 1 patient with neutropenia, and 1 patient with flu-like symptoms. One patient experienced a pulmonary embolism and one patient had a portal vein thrombosis. Common Grade 2 toxicities included fatigue (21%), cytopenias (21%) and GI side effects (16%). There was no treatment-related mortality. Conclusions: These data support the efficacy of the RITE regimen, and the possibility of using alternative Bcl-2 modulating agents in combination with docetaxel in future studies. In addition, long term treatment with low dose docetaxel may be feasible. The assessment of an effect on PBMC Bcl-2 expression is ongoing. No significant financial relationships to disclose.