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Purpose Weekly paclitaxel, concurrent radiation, and androgen deprivation (ADT) were evaluated in patients with high-risk prostate cancer (PC) with or without prior prostatectomy (RP). Methods and Materials Eligible post-RP patients included: pathological T3 disease, or rising prostate-specific antigen (PSA) ≥0.5 ng/mL post-RP. Eligible locally advanced PC (LAPC) patients included: 1) cT2b-4N0N+, M0; 2) Gleason score (GS) 8–10; 3) GS 7 + PSA 10–20 ng/mL; or 4) PSA 20–150 ng/mL. Treatment included ADT (4 or 24 months), weekly paclitaxel (40, 50, or 60 mg/m 2 /wk), and pelvic radiation therapy (total dose: RP=64.8 Gy; LAPC=70.2 Gy). Results Fifty-nine patients were enrolled (LAPC, n = 29; RP, n = 30; ADT 4 months, n = 29; 24 months, n = 30; whites n = 29, African Americans [AA], n = 28). Baseline characteristics (median [range]) were: age 67 (45–86 years), PSA 5.9 (0.1–92.1 ng/mL), GS 8 (6–9). At escalating doses of paclitaxel, 99%, 98%, and 95% of doses were given with radiation and ADT, respectively, with dose modifications required primarily in RP patients. No acute Grade 4 toxicities occurred. Grade 3 toxicities were diarrhea 15%, urinary urgency/incontinence 10%, tenesmus 5%, and leukopenia 3%. Median follow-up was 75.3 months (95% CI: 66.8–82.3). Biochemical progression occurred in 24 (41%) patients and clinical progression in 11 (19%) patients. The 5- and 7-year OS rates were 83% and 67%. There were no differences in OS between RP and LAPC, 4- and 24-month ADT, white and AA patient categories. Conclusions In addition to LAPC, to our knowledge, this is the first study to evaluate concurrent chemoradiation with ADT in high-risk RP patients. With a median follow-up of 75.3 months, this trial also represents the longest follow-up of patients treated with taxane-based chemotherapy with EBRT in high-risk prostate cancer. Concurrent ADT, radiation, and weekly paclitaxel at 40 mg/m 2 /week in RP patients and 60 mg/m 2 /week in LAPC patients is feasible and well-tolerated.

Purpose We report the long-term results of a prospective, Phase II study of long-term androgen deprivation (AD), pelvic radiotherapy (EBRT), permanent transperineal prostate brachytherapy boost (PB), and adjuvant docetaxel in patients with high-risk prostate cancer. Methods and Materials Eligibility included biopsy-proven prostate adenocarcinoma with the following: prostate-specific antigen (PSA) > 20 ng/ml; or Gleason score of 7 and a PSA >10 ng/ml; or any Gleason score of 8 to 10; or stage T2b to T3 irrespective of Gleason score or PSA. Treatment consisted of 45 Gy of pelvic EBRT, followed 1 month later by PB with either iodine-125 or Pd-103. One month after PB, patients received three cycles of docetaxel chemotherapy (35 mg/m 2 per week, Days 1, 8, and 15 every 28 days). All patients received 2 years of AD. Biochemical failure was defined as per the Phoenix definition (PSA nadir + 2). Results From August 2000 to March 2004, 42 patients were enrolled. The median overall and active follow-ups were 5.6 years (range, 0.9–7.8 years) and 6.3 years (range, 4–7.8 years), respectively. Grade 2 and 3 acute genitourinary (GU) and gastrointestinal (GI) toxicities were 50.0% and 14.2%, respectively, with no Grade 4 toxicities noted. Grade 3 and 4 acute hematologic toxicities were 19% and 2.4%, respectively. Of the patients, 85.7% were able to complete the planned multimodality treatment. The 5- and 7-year actuarial freedom from biochemical failures rates were 89.6% and 86.5%, and corresponding rates for disease-free survival were 76.2% and 70.4%, respectively. The 5- and 7-year actuarial overall survival rates were 83.3% and 80.1%, respectively. The 5- and 7-year actuarial rates of late Grade 2 GI/GU toxicity (no Grade 3–5) was 7.7%. Conclusions The trimodality approach of using 2 years of AD, external radiation, brachytherapy, and upfront docetaxel in high-risk prostate cancer is well tolerated, produces encouraging long-term results, and should be validated in a multi-institutional setting.