Prospective Trial Of Escalating Doses Of Paclitaxel, Concurrent Radiation And Androgen Deprivation In High-Risk Prostate Cancer With Or Without Prior Prostatectomy

To evaluate the tolerability and efficacy of weekly paclitaxel, concurrent radiation and androgen deprivation (ADT) in patients with high risk prostate cancer (PC) with or without prior prostatectomy (RP). For this prospective trial, eligible post-RP patients included pathological T3 disease or rising PSA ≥ 0.5ng/ml post-RP. Eligible locally-advanced PC (LAPC) patients included: 1) cT2b-4N0N+, M0; 2) Gleason Score (GS) 8-10; 3) GS 7 + PSA 10-20ng/ml; or 4) PSA 20-150ng/ml. Treatment included ADT (4 or 24 months), weekly paclitaxel [40 (n = 10), 50 (n = 31), or 60mg/m2/wk (n = 18)], and pelvic radiation therapy (total dose: RP = 64.8 Gy; LAPC = 70.2 Gy). Acute and late toxicities were graded via the CTC and modified RTOG-LENT scales, respectively. The freedom from biochemical failure rates were computed using the Phoenix definition (PSA nadir + 2ngm/ml) for LAPC and PSA > 0.5ng/ml for RP patients. Between October 1999 and July 2006, 59 patients were enrolled [LAPC (n = 29), RP (n = 30); ADT: 4 months (n = 29), 24 months (n = 30); Race: Whites (n = 29), African Americans [AA] (n = 28); N+ (n = 7)]. The median follow-up was 75.3 months (range, 7-103 months; 95% CI: 66.8-82.3 months). Baseline characteristics [median, (range)] were: age 67 (45-86 years), PSA 5.9 (0.1-92.1ng/ml), GS 8 (6-9). At escalating doses of paclitaxel, 95-98% of doses were given with radiation and ADT, 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%), leukopenia (3%). Only 5% experienced late grade 3 (n = 2) or 4 (n = 1) GI/GU toxicities. Biochemical progression occurred in 24 (41%) patients, clinical progression in 11 (19%) patients. The 5- and 7-year OS rates were 83% and 67%, respectively. There were no differences in OS between RP and LAPC, 4- and 24-month ADT, White and AA patient categories. With a median follow-up of 75.3 months, this trial represents the longest follow-up of patients treated with concurrent taxane-based chemotherapy with EBRT in men with high risk prostate cancer. Concurrent ADT, radiation and weekly paclitaxel at 40mg/m2/wk in RP patients and 60mg/m2/wk in LAPC patients is feasible and well-tolerated.