A new paradigm for the treatment of high-risk prostate cancer: radiosensitization with docetaxel

Abstract

Survival and biochemical outcome of patients with localized, high-risk prostate cancer treated with definitive three-dimensional conformal radiation therapy (3-D CRT) with or without hormonal therapy are poor. Other therapeutic strategies are needed to improve outcome in these poor-prognostic-group patients. One such strategy involves the use of chemotherapeutic agents to radiosensitize the effects of local 3-D CRT. Very few investigators have tested this novel concept of chemotherapeutic radiosensitization. Two studies evaluated the combination of estramustine phosphate and vinblastine (EV) with radiation therapy (RT). In both studies, the combination of EV and RT resulted in moderate to severe acute and late toxicity. A recently completed, phase I trial evaluated the maximally tolerated dose (MTD) of weekly docetaxel that could be concurrently delivered with 3-D CRT (70.2 Gy) in men with high-risk prostate cancer. The MTD of concurrent weekly docetaxel with 3-D CRT was determined to be 20 mg/m(2), and this combination was shown to be safe and well tolerated. This was the first trial to evaluate taxane radiosensitization in prostate cancer. Other phase I/II studies are needed to further assess chemotherapeutic radiosensitization in localized, high-risk prostate cancer.

Figures

Figure 1

Schema for a phase I trial of docetaxel and three-dimensional conformal radiation therapy (3-D CRT) for the treatment of men with high-risk, localized prostate cancer. Rx, treatment; PSA, prostate-specific antigen; MTD, maximally tolerated dose.