Phase I Trial of Weekly Docetaxel, Total Androgen Blockade, and Image-Guided Intensity-Modulated Radiotherapy for Localized High-Risk Prostate Adenocarcinoma

This phase I trial provided the maximum tolerated dose (MTD) of 25 mg/m(2) for docetaxel when combined with androgen deprivation therapy (ADT) and high-dose intensity-modulated radiotherapy (IMRT) to the prostate and seminal vesicles for high-risk localized prostate cancer. No patients had severe side effects at this dose, and it should be used in future trials to test the efficacy of this treatment paradigm. Background: This was a phase I study to find the maximum tolerable dose (MTD) of weekly docetaxel combined with high-dose intensity-modulated radiotherapy (IMRT) and androgen deprivation therapy (ADT). Patients and Methods: Men with localized high-risk prostate cancer (HRPC) were treated with weekly docetaxel at 10 to 30 mg/m2 concurrent with IMRT of 77.4 Gy to the prostate and 45 Gy to the seminal vesicles. ADT consisted of a gonadotropin-releasing hormone agonist (GnRHa) and bicalutamide beginning 2 months before and during chemoradiation. GnRHa was continued for 24 months. Results: Nineteen patients were enrolled. No dose-limiting toxicity (DLT) was seen with docetaxel doses up to 25 mg/m(2). At the 30 mg/m(2) level, 2 of 4 patients experienced DLTs of both grade 3 fatigue and dyspepsia. At 41 months' median follow-up, 2 patients had died-1 from metastatic prostate cancer and the other from heart failure. Two other patients experienced biochemical failure. One patient with bladder invasion at diagnosis experienced late grade 2 urinary hesitancy 9 months after completion of radiotherapy, requiring short-term intermittent catheterization. All patients had erectile dysfunction, but no late toxicities worse than grade 2 were identified. Conclusion: Weekly docetaxel may be combined with high-dose IMRT and long-term ADT up to a MTD of 25 mg/m2. Acute toxicities and long-term side effects of this regimen were acceptable. Future studies evaluating the efficacy of docetaxel, ADT, and IMRT for localized HRPC should use a weekly dose of 25 mg/m(2) when limiting the irradiated volume to the prostate and seminal vesicles. (C) 2014 Elsevier Inc. All rights reserved.