Phase II trial of fulvestrant in castration resistant prostate cancer

Abstract

16079 Background: Preclinical evidence supports the role of estrogen receptor signaling in prostate cancer. In this phase II trial we investigated the tolerability and efficacy of fulvestrant, a pure estrogen receptor antagonist, in the treatment of castration resistant prostate cancer (CRPC). Methods: Patients with CRPC were enrolled after written informed consent. Fulvestrant was administered at a dose of 500 mg by intramuscular injection on day 0, then 250 mg intramuscularly on day 14, day 28 and monthly. History, physical examination, serum prostate specific antigen (PSA) levels and toxicity was evaluated monthly. Computed tomography and bone scan were repeated every 3 months to assess disease. Treatment was continued until disease progression, unacceptable toxicity, non-compliance or consent withdrawal. Results: Twenty patients were enrolled over a period of six months. All patients were Caucasians with median age of 69.5 years [range: 47–85 years]. Sixteen patients (80%) patients had radiological evidence of metastasis and 4 patients (20%) had rising PSA as the only evidence of progressive disease. The median PSA was 41.4 ng/ml (range: 7.1–933.5). Patients received a median of 3 treatment cycles of fulvestrant [range: 1–11]. Median time to progression was 4.3 months (95% confidence interval of 3 to 5.7 months) and median overall survival was 19.4 months (range: 9.9–19.4 months) after a median follow-up of 16 months. No patient showed ≥50% reduction in PSA or radiologic improvement. Few adverse events were noted, none of which were attributed directly to fulvestrant. Conclusion: Fulvestrant was well tolerated but failed to produce clinical or PSA response in men with CRPC. Treatment received, outcome and survival Complete/partial response 0 Stable disease 16 (80%) Progressive disease 4 (20%) Time to progression (median; range) 4.3 months (3-5.7) Off treatment reason: Treatment ineffective 2 (10%) PSA progression 12 (60%) Bone progression 6 (30%) Soft tissue progression 2 (10%) Median cycles completed 3 (1–11) Dose delays 2 Median survival (months) 19.4 Median follow-up (months) 16 Deaths 3 (15%) Two patients went off treatment with both bone and soft tissue progression. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca Oncology