SWOG 99–16: Randomized phase III trial of docetaxel (D)/estramustine (E) versus mitoxantrone(M)/prednisone(p) in men with androgen-independent prostate cancer (AIPCA)

3 Background: The median survival of AIPCA patients (pts) treated with M+P is 10–12 months. Phase I/II trials of AIPCA pts treated with D+E reported survivals of 20–23 months. SWOG 99–16 was designed to compare the survival D+E to M+P. Methods: 770 men with progressive AIPCA were randomized to either Arm 1) Dexamethasone 60 mg premedication; D=60 mg/m2 day(D) 2, E= 280 mg PO D1–5 Q 21 D or Arm 2) M 12 mg/m2 + P 5 mg PO BID q 21 D. Pts were dose escalated to 70 mg/m2 in Arm 1 and 14 mg/m2in Arm 2 if no Grade(G) 3 or 4 toxicities were observed in cycle 1. Assuming 310 eligible pts in each arm, the study had 0.80 power to detect a 33% difference in survival. All p-values reported are two-sided. Results: Pt Characteristics: Eligible pts Arm 1:334; Arm 2 :332. Pretreatment characteristics were equally balanced for age, race, performance status, PSA and symptoms. Response and Survival: The median survival of men treated on Arm 1 was 18 months and Arm 2 was 15 months (logrank p=.008). The hazard ratio was 0.77 (95% confidence interval 0.64, 0.94). Arm 1 also demonstrated a superior median time to progression (6 months) compared to Arm 2 (3 months) logrank p<0.0001. The measurable disease response rates in Arm 1 and 2 were 17% and 10% (p=.30), respectively. Toxicity: G 3 or 4 toxicity was reported in 175 pts (54%) on Arm 1 and 109 pts (34%) on Arm 2, due to higher rates of gastrointestinal (63pts vs. 21pts) and cardiovascular (44pts vs 20pts) events on Arm 1. There was no significant difference in toxic deaths observed Arm 1 (n=7, 2%) vs. Arm 2 (n=4, 1%). Conclusions: The 23% improvement in survival in men treated with D+E supports its use as first line therapy for AIPCA. This is the first large randomized trial demonstrating a survival advantage in AIPCA. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis