[2006] [1589] ADJUVANT WEEKLY DOCETAXEL FOR HIGH-RISK PROSTATE CANCER PATIENTS AFTER RADICAL PROSTATECTOMY.

Adam S Kibel*, St. Louis, MO; Micahel W. Kattan, Cleveland, OH; Joel Picus, St. Louis, MO; Robert Dreicer, Eric Klein, Cleveland, OH; George Wilding, David Jarrard, Madison, WI; Bruce Roth, Michael Cookson, Nashville, TN; Daniel Petrylak, New York, NY; Gurkamal Chatta, Joel Nelson, Pittsburgh, PA; Tomasz Beer, Portland, OR; Robert DiPaola, New Brunswick, NJ; Alan Partin, Eli Rosenbaum, Elizabeth Garrett, Elizabeth Sugar, Mario Eisenberger, Baltimore, MD.

Introduction and Objective: Radical prostatectomy (RP) is an effective treatment for localized prostate carcinoma (PCa). Unfortunately, patients with adverse pathologic features (i.e. positive lymph nodes, positive seminal vesicles, positive margins), have a high risk of recurrence. In an effort to improve outcomes in this population we conducted a phase II study of post RP adjuvant docetaxel in patients at high risk for recurrence after RP. Herein, we report our toxicity and progression-free survival (PFS) data. Methods: Patients with confirmed PCa, S/P RP within 3 months, without distant metastases, organ dysfunction, prior RT or systemic treatment were eligible. Pathology was centrally reviewed and risk assessment was based on a validated multivariate Cox proportional hazards model (Roberts, Urology, 2001). Greater than 50% risk of recurrence by 3 years was required for eligibility. Docetaxel 35mg/m² was given at days 1, 8, 15 of a 28 day cycle x 6 cycles starting 4-12 weeks following surgery. Recurrence was defined as PSA (>0.2ng/ml) or radiologic/pathologic evidence of metastatic disease. Predicted PFS for each patient were calculated using the Cox model from a validated nomogram (Kattan, JCO, 1999) and then compared to actual PFS. Results: 77 patients were registered between 2/02-12/03. All patients completed treatment. Pathology demonstrated positive seminal vesicles in 50/77 (65%), positive lymph nodes in 22/77 (29%) and positive margins in 50/77 (65%). Gleason score was 7, 8, 9 and 10 in 44%, 13%, 39% and 3% of patients, respectively. At median follow-up of 28 months, 47 of 75 evaluable patients (63%) progressed. Median PFS was 16.3 months (95% CI 13.0-19.8 months). Predicted PFS was 10.0 months. Seven patients died; 4 of prostate cancer. Grade I/II toxicity in the absence of grade III/IV toxicity occurred in 54 (70%) of patients. Grade III toxicity occurred in 20 (26%) of patients and included hyperglycemia, dyspnea, cardiac arrhythmias and pulmonary fibrosis. Grade IV toxicity was hyperglycemia in 2 patients which resolved, and a GI bleed resulting in death in one patient which was possibly related to treatment. One patient with grade III pulmonary fibrosis died of pneumonia 556 days following treatment which may have been related to docetaxel. Conclusions: Adjuvant docetaxel for PCa is feasible with significant but acceptable toxicity in a high risk population. Actual PFS appears to be longer than predicted by a nomogram. Given docetaxel’s success in treating hormone refractory PCa, an adjuvant Phase III trial has been initiated.

Discussed Poster: Prostate Cancer: Localized (III) (1:00 PM-4:00 PM)