A pilot multicenter phase II study of adjuvant docetaxel (D) for high risk prostate cancer (PC) patients (pts) after radical prostatectomy (RP): Preliminary data

Abstract

4565 Background: We conducted a pilot adjuvant D study in pts at high risk for recurrence after RP. Study objectives were to evaluate: 1. toxicity 2. feasibility of 6 months of adjuvant D treatment and 3. Incidence of PSA relapses (>0.2ng/ml) in 2 and 3 years (vs. matched controls). Methods: Eligible pts had confirmed PC, within 3 months of RP, without distant metastases, organ dysfunction or prior RT or systemic treatment. Pathology was centrally reviewed (JHU). Risk was assessed based on a multivariate Cox proportional hazards model (Rw’ = lymph node (0/1)*1.43 + seminal vesicle (0/1)*0.51 + surgical margin (0/1)*1.15 + modified Gleason score (MGS) (0–4) * 0.71) [MGS: Gleason 5=0; 3+3=1; 3+4=2; 4+3=3; 8–10=4]. The minimum value for study entry was based on a projected 50% rate of recurrence by 3 years = Rw’ > 2.84. (Roberts et al Urology 2001). Treatment included 6 cycles of IV D 35mg/m2 on days 1, 8, 15 of a 28 day cycle starting 4–12 weeks after surgery. We have 90% power to detect a 3-year progression free survival rate of 69% versus the control rate of 50%, α=0.05. Results: 77 pts with a median age of 60(43–76) and median Rw’ of 4.07 (2.85–5.93) were enrolled (4/02–1/04). Treatment was well tolerated and all pts completed treatment. Hyperglycemia was the only grade IV toxicity (2.6%). Grade III: hyperglycemia 7.7%, dyspnea 5.2%, leukopenia 3.9%. 5 pts required dose reduction (LFT’s), and 6 Rx delay. One death probably unrelated to D. Grade I/II (>30%) included the common D toxicities being mostly mild and reversible. With a median f/u of 17m (10–31), the median time to PSA relapse was not reached. 3 pts developed distant metastases and 2 pts died from progressive disease. Comparison of outcome with pathologically and clinically matched historical controls (JHU) is needed and is currently in progress and ongoing. Conclusions: These data suggest that post operative adjuvant weekly D is feasible, well tolerated and has only moderate reversible toxicity. Based on recent reports of improved survival with D in HRPC, further evaluation of D (and hormonal therapy) in a phase III in the adjuvant setting is warranted. (Supported by Aventis). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis