Weekly docetaxel plus estramustine for hormone-refractory prostate cancer (HRPC) with intermittent repetition: Preliminary results of a multicenter phase II study (AUO AP33/02)

Abstract

4613 Background: Docetaxel is active in HRPC alone, with prednisone, and with estramustine. We investigated whether tumor control can be maintained with intermittent docetaxel-estramustine, which may have a favorable toxicity profile compared with standard dosing. Methods: Patients with HRPC and prostate-specific antigen (PSA) or clinical progression received weekly docetaxel 35 mg/m2 (30-minute intravenous infusion on Days 2, 9, and 16) with estramustine (140 mg orally, tid on Days 1–3, 8–10, and 15–17). Treatment was interrupted after 3 cycles (1 sequence) and monthly follow-up visits were performed (to assess PSA level, pain scores, white blood cell count). Treatment was restarted if PSA levels doubled (compared with the nadir during the previous sequence) or if progression was suspected for other reasons. The primary endpoint was best response (clinical and/or PSA) to treatment in Sequence 2. PSA response was defined as a ≥50% reduction in PSA from baseline, lasting ≥ 4 weeks. Assuming that 60% of enrolled patients would start Sequence 2 and a PSA response rate of 70%, ≥67 patients were required to confirm a response rate ≥50% (0.05 1-tailed type I error; 80% power). Results: Seventy-five patients (median age 66; range: 50–88 years) have been enrolled. Baseline ECOG PS was 0–1 in 95% of patients. Sequences 2/3/4 were started in 40/23/7 patients, respectively, and the median treatment-free intervals were 86.5/86.0/75.0 days. PSA levels were 105/96/179/232 ng/mL at the start of Sequences 1/2/3/4, respectively; PSA response (90% CI) was achieved in 76% (67–84%), 80% (67–90%) [primary endpoint], 57% (38–74%), and 29% (5–66%) of patients, respectively. Median follow-up was 9.1 (range: 0.7–21) months. So far, 21 patients (28%) have died. Main WHO grade 3–4 toxicities were: leukocytopenia (6.7%), pain (14.7%), and nail changes (5.3%). Conclusions: Intermittent docetaxel and estramustine is well tolerated and shows a high response rate in the second and third sequence of treatment in patients with HRPC. Further evaluation vs continuous treatment is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis, AstraZeneca AstraZeneca