Analysis of Late Toxicity of a Phase I/II Trial of Weekly Paclitaxel, Concurrent Radiation (RT) and Androgen Ablation (AA) in Locally Advanced Prostate Cancer (LAPC) or after Radical Prostatectomy (RP)

Abstract

To determine prospectively the acute and late gastrointestinal (GI) and genitourinary (GU) toxicity of RT concurrent with weekly paclitaxel and AA in locally advanced prostate cancer (LAPC) or after RP. Eligible patients included those with M0 disease and (a) pT3 tumors, (b) rising PSA post-RP, (c) N1 disease, (d) Gleason score (GS) ≥8 (biopsy or RP), (e) PSA ≥20 but ≤150, or (f) GS ≥7 and PSA ≥10. Androgen deprivation was started 72 hr before the first paclitaxel infusion, which was given at a dose of 40mg/m2 (n = 11), 50mg/m2 (n = 39), or 60mg/m2 (n = 9) for 7 weeks. LHRH agonists were continued for 2 years in patients with GS ≥8 or N1 cancer; all others received 4 months of AA. RT started 1 day after the first paclitaxel infusion. A dose of 45Gy was delivered to the whole pelvis. Post-RP patients received a 19.8Gy boost to the prostate bed (total 64.8Gy); LAPC patients received a 25.2Gy boost to the prostate (total 70.2Gy). Acute toxicity was scored using the Common Toxicity Criteria Version 3.0; late toxicity was graded with the modified RTOG-LENT scale. 59 patients were enrolled; 58 are evaluable for late toxicity. Median age was 67 (range 44-86). Thirty patients were treated post-RP; 29 were treated for LAPC. Median follow-up was 56 months (range 3-96). Acute GI toxicity rates were 47% (grade 2) and 5% (grade 3). Acute GU toxicity occurred in 14% (grade 2) and 8% (grade 3). There were no cases of acute grade 4 GI or GU toxicity. The actuarial rate of late grade 2 GI toxicity at 1, 2 and 5 years was 5%, 7%, and 9%, respectively. There was 1 case of late grade 4 large bowel obstruction. The actuarial rate of late grade 2-3 GU toxicity at 1, 2, and 5 years was 4%, 5%, and 7%, respectively. There were no cases of late grade 4 GU toxicity. There was no difference in toxicity between post-RP patients and those treated for LAPC. To our knowledge, this is the largest prospective series with the longest follow-up of high-risk patients treated with AA, concurrent RT and weekly taxane-based chemotherapy. This trimodality treatment proved to be well-tolerated and associated with a low rate of late grade ≥2 GI and GU toxicity.