Adjuvant docetaxel chemotherapy with abbreviated hormonal therapy in patients with high-risk prostate cancer

Abstract

15589 Background: We conducted a pilot adjuvant docetaxel and abbreviated androgen deprivation study (ADT) in patients with high-risk localized prostate cancer. Study objectives were to evaluate toxicity, feasibility of 6 months of ADT and 3 months of docetaxel treatment, and incidence of serum PSA relapse at 2 years compared to historical controls. Methods: Eligible patients had radical prostatectomy or radiation therapy for high-risk disease (pathologic node positive disease, capsule involvement, extra-capsular extension, seminal vesicle involvement, positive surgical margins, Gleason score = 8, clinical stage T2c or T3, serum PSA >20, or pre-op PSA > 15 plus any high-risk feature). Patients were treated with taxotere 35 mg/m2 weekly 3 out of every 4 weeks for 3 months, and an LHRH analog for 6 months concurrently. In this high-risk cohort, we estimated the risk of PSA recurrence to be as high as 65% in 2 years. To detect a reduction in recurrence rates after surgery or radiation by 40% at a power of 80% and a 2-sided alpha of 0.05, a total of 21 patients were needed in this pilot Phase II study. Results: Twentyone patients were enrolled between 9/04–9/05. The median age was 59.5 years (48–72). Ten patients had a radical prostatectomy and 11 had radiation therapy. All patients received 6 months of LHRH analog therapy. Median pre- treatment PSA was 9.5 ng/ml (4–120). Mean Gleason grade was 8 (7–9); 65% of the patients had >50% biopsies positive. Treatment was well tolerated. Acute toxicity included 1 grade IV hyperglycemia. There was 1 dose reduction and 1 treatment delay. One patient had grade III elevation in serum AST which was transient. Grade I/II toxicities were common and included fatigue, diarrhea, insomnia, and pedal edema. Median follow up is 20 months. Five patients have relapsed. One (of 11) patients treated with radiation has relapsed with metastatic bone disease at 9 months. Four (of 10) patients who underwent prostatectomy have had a serologic relapse at 14, 14, 17 and 21 months, respectively. Conclusions: These data suggest that adjuvant weekly taxotere with abbreviated course of ADT is feasible and well tolerated. In this pilot trial, at a median follow up of 20 months, 23% of patients have relapsed. Longer follow up is required and is ongoing. No significant financial relationships to disclose.