Outcome of patients with non-metastatic versus metastatic hormone refractory prostate cancer (HRPC) treated with second-line hormonal therapy consisting of ketoconazole (keto) plus granulocyte macrophage colony stimulating factor (GM-CSF)

Abstract

4626 Background: Second line hormonal manipulations are frequently used in pts with HRPC. It is unknown if these manipulations are more effective in patients without clinical metastases. The efficacy of a second-line hormonal manipulation (keto plus GM-CSF) was prospectively evaluated in a cohort of HRPC patients with and without metastases. Methods: Eligible pts had progressive HRPC by consensus criteria, no prior immunotherapy, chemotherapy or keto. Pts received keto 400 mg po tid and hydrocortisone 20 mg po qAM and 10 mg po qPM. GM-CSF 250 mcg/m2 was administered SQ on days 15–28 of each 28-day cycle. Results: Forty-two of 48 planned pts have been enrolled, 30 with clinical metastases, 12 with PSA-only disease and are evaluable for PSA response, using consensus criteria. The median age is 68 years (range: 53–84), and median PSA 23.1 ng/mL (range: 5.4–306.5). The median treatment duration is 5.1 months (range: 0.3–22+). Overall, 30 of 43 patients (69%) have experienced a ≥ 50% reduction in PSA. The PSA response proportion in the non-metastatic patients is 8/12 (66%) while the response proportion in those with metastases is 16/30 (53%, chi squared p = 0.41). Twenty-three patients have discontinued therapy after a median of three cycles. Progressive disease has occurred in 17 patients, 3 of 12 patients with non-metastatic disease and in 14 of 30 patients with metastatic disease (25% vs. 47%, chi squared p=0.20). Six patients have discontinued due to toxicity or patient choice. The primary endpoint of the study, overall time to progression, has not been reached at a median follow up of 7 months. Conclusions: There was no significant difference in response proportion and progressive disease rate in HRPC patients with and without metastatic disease treated with keto/GM-CSF. While these data require prospective confirmation in a larger group of patients, they suggest that secondary hormonal manipulations are warranted in either patient group. No significant financial relationships to disclose.