A phase III protocol of androgen suppression (AS) and radiation therapy (RT) versus AS and RT followed by chemotherapy with paclitaxel, estramustine, and etoposide (TEE) for localized, high-risk, prostate cancer, RTOG 9902.

Abstract

4632 Background: High-risk, localized prostate cancer (PCa) is generally treated with a combination of RT and long-term AS. It was our hypothesis that adjuvant CT would improve the survival rate of high-risk PCa when used in combination with RT and AS. Methods: Pts with PSA 20-100 and Gleason score (GS) ≥7 or clinical stage ≥T2 and GS ≥8 were randomized to RT and AS with or without four 21-day cycles of CT, starting 28 days after RT, with oral estramustine 280 mg tid × 14 days, oral VP-16 50 mg/m2 in divided doses bid × 14 days, and paclitaxel 135 mg/m2 iv on day 2. Warfarin was originally given at 1 mg/day during CT, but, after thromboembolic (TE) toxicity was observed, the dosage was increased to keep the INR between 1.5 and 2.5. RT consisted of 46.8 Gy to a small pelvic field followed by a prostate boost of 23.4 Gy for a total of 70.2 Gy. AS consisted of LHRH for 24 mos beginning 2 mos preRT plus oral antiandrogen before and during RT. Results: This study opened in Jan 2000 and closed in Oct 2004 with a total of 397 pts (of a planned 1,440) entered (380 eligible). We previously reported on the TE toxicities that led to early protocol closure (Rosenthal, et al. IJROBP 73:672, 2009), but pts have been followed for the primary endpoint, and we report now overall survival (OS) as well as biochemical failure (BF). Pts had high-risk features: 68% had GS ≥8, median PSA was 24.2, and 33% were cT3. Median FU is 6 yrs. 5-yr OS was 86% for both the RT+AS and RT+AS+CT arms (p=0.79). 5-yr BF rates were also similar: 43% for RT+AS and 48% for RT+AS+CT (p=0.26). Conclusions: RTOG 9902 failed to reach its accrual goal due to toxicity. With 5-yr data, there is no difference in OS observed with the addition of adjuvant CT. No difference in 5 yr BF rates was noted. Sample size reduction because of premature closure may have reduced the ability to detect a significant difference. A similarly designed trial, RTOG 0521, completed accrual in 2009, but CT was delivered with docetaxel/prednisone rather than TEE. Results of RTOG 0521 are pending and may help better define the role for adjuvant CT for high risk, localized PCa pts. Supported by NCI grants U10 CA21661 and U10 CA37422. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Bristol-Myers Squibb, Ferring Pharmaceuticals, Watson Pharmaceuticals Bristol-Myers Squibb