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

Abstract

<h3>Purpose/Objective(s)</h3> In high-risk localized prostate cancer (HRLPC), the standard of care is dose-escalated radiation therapy (DERT) with long-term androgen deprivation therapy (LTADT). Unfortunately, outcomes are less than ideal. There is significant interest in improving outcomes by intensifying treatment for these patients using docetaxel (D). This phase I study was designed to find the maximum tolerable dose (MTD) of concurrent weekly D when combined with DERT to the prostate with long-term androgen deprivation therapy (LTADT) in HRLPC patients. Initial results reported demonstrated a MTD for docetaxel of 25 mg/m² with acceptable toxicities. Here we describe the long-term outcomes in these patients. <h3>Materials/Methods</h3> We enrolled 19 patients with HRLPC (≥1 of ≥cT2c, PSA ≥20ng/ml, or Gleason ≥8) on this phase 1 study. Patients received neoadjuvant combined androgen blockade for 2 months and then during radiation of 77.4 Gy to the prostate and 45 Gy to the seminal vesicles with concurrent weekly D. No pelvic/nodal radiotherapy was given. D was administered in a standard dose-escalated scheme requiring ≥3 patients per cohort, starting at 10mg/m² and increasing to 30mg/m² in 5mg/m² increments. The GnRH agonist was continued for an additional 24 months. The primary objective of the study was to determine the MTD of D in combination with DERT and LTADT. Secondary end points included progression free survival (PFS), metastasis free survival (MFS) and overall survival (OS). Kaplan-Meier analysis was used to estimate the survival probabilities. <h3>Results</h3> MTD was found to be 25mg/m². There was no grade ≥3 toxicity at this or lower dose levels. At a median follow up of 10.5 years the median OS was not reached. 5-year and 10-year OS was found to be 89.5% and 68.4%, respectively. Median MFS was found to be 11.3 years with 5- and 10-year MFS of 84.2% and 57.9%. Median PFS was 9.0 years with 73.7% and 42.1% at 5 and 10 years, respectively. <h3>Conclusion</h3> In the setting of high-dose IMRT to the prostate with concurrent LTADT the MTD of concurrent weekly docetaxel is 25mg/m². This study showed a 5-year OS of 89.5% with a median OS not reached with > 10 years of follow-up. This mature data suggests that the addition of concurrent weekly docetaxel at 25mg/m² to high-dose IMRT to the prostate is safe and may provide cancer control rates similar to those recently reported for adjuvant full-dose D.