5004 Introduction: Prostate cancer patients in the noncastrate state with a rapidly rising PSA are at high-risk for cancer-specific mortality. Since hormonal therapy alone is not curative, we have explored the use of rapid androgen cycling with Doc to recruit proliferating cells into successive waves of apoptosis, thereby shifting the treatment outcome for these patients from palliation to cure. Methods: Patients with noncastrate levels of testosterone (T), a rising PSA ± metastases, and = 6 months of prior hormones were eligible. Cohort 1: Six 4- week cycles of monthly leuprolide and Doc (75 mg/m2), with 7 days of topical T repletion (AndroGel 1% 5G) prior to each treatment. Cohort 2: Nine 3-week cycles of Doc (70 mg/m2), with 3 days of T repletion per cycle and 3-month depot leuprolide on day 1 of cycles 1, 5, and 9. The primary endpoint was the proportion of patients with a treatment-specific undetectable PSA at 6 and 18 months defined as: = 0.05 after surgery, = 0.5 after radiation, or = 2.0ng/ml with untreated disease. This is based on the premise that an undetectable PSA is a prerequisite to, but no guarantee of cure. Results: There were no increases in sequential PSA peaks or troughs and 100 out of 102 patients completed the planned 6 months of chemohormonal treatment. Twenty three of 62 (37%) patients in cohort 1, and 25 of 38 (66%) patients in cohort 2 achieved the primary endpoint of a treatment-specific undetectable PSA at 6 months. At 12 months, no patient in cohort 1 had maintained an undetectable PSA in the setting of a noncastrate T level; whereas, 8 of 15 (53%) patients in cohort 2 have achieved the endpoint at 12 months. Toxicities were similar to those observed with Doc and hormonal therapy administered separately. Conclusions: Rapid androgen cycling with docetaxel is feasible, and can induce successive declines in PSA peaks and troughs. The more dose-dense cohort 2 schedule of 21-day Doc administration for 9 cycles, along with reduced exposure to androgen repletion from 7 to 3 days, has resulted in a higher proportion of undetectable PSA outcomes at both 6 (66% vs. 37%) and 12 (53% vs. 0%) months. Complete PSA outcomes for cohort 2 at 12 and 18 months are still pending. Supported by Sanofi-Aventis, CA-05816, and PepsiCo. No significant financial relationships to disclose.