{'fraction_non_alphanumeric': 0.035379369138959935, 'fraction_numerical': 0.028985507246376812, 'mean_word_length': 4.838308457711443, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Phase I trial of total androgen blockade, weekly docetaxel, and image-guided intensity-modulated radiotherapy for localized high-risk prostate adenocarcinoma.

96 Background: High-risk prostate cancer patients have high rates of treatment failure and improved outcomes are needed. Docetaxel has shown efficacy in hormone-resistant prostate cancer and can act as a radiosensitizer. Dose escalation studies with radiation therapy have found improved freedom from failure rates. The addition of androgen deprivation therapy (ADT) improves overall survival. Therefore, this phase I study was designed to find the maximum tolerable dose (MTD) of weekly docetaxel when combined with high-dose image-guided intensity-modulated radiotherapy (IGRT) and ADT in patients with high-risk prostate cancer.


METHODS
Men with high-risk adenocarcinoma of the prostate (≥T2c, or PSA ≥20ng/ml, or Gleason ≥8) were treated with weekly docetaxel (given at 10-30 mg/m2, increasing by 5 mg/m2until the MTD was reached) concurrently with IGRT of 77.4 Gy in 43 fractions to the prostate and 45 Gy in 25 fractions to the proximal seminal vesicles. ADT consisted of a gonadotropin-releasing hormone agonist (GnRHa) and bicalutamide beginning 2 months before chemoradiation and continuing 2 months concurrently. The GnRHa was then continued for an additional 24 months.


RESULTS
19 patients began combined chemoradiation between April 2006 and December 2010. Median follow-up is 32 months. No dose-limiting toxicities (DLTs) were seen in patients treated with docetaxel doses up to 25 mg/m2. However, at the 30 mg/m2level, 2 of 4 patients experienced DLTs of both grade 3 fatigue and grade 3 upper GI toxicity, indicating the MTD had been exceeded. At last follow-up, 2 patients had died, one from metastatic prostate cancer and the other from heart failure. A second patient demonstrated biochemical failure by the Phoenix criteria at 46 months, giving an actuarial biochemical disease-free survival (bDFS) at 3 years of 94.7%. All patients had ≥grade 2 erectile dysfunction but no other ≥grade 2 long-term toxicities were identified.


CONCLUSIONS
Weekly docetaxel may be combined with high-dose IGRT and long-term ADT up to a MTD of 25 mg/m2. Long-term side effects with this regimen were minimal, and bDFS rate is encouraging.


CLINICAL TRIAL INFORMATION
NCT00099086.