Ketokonazol/hydrocortisone versus estramustinphosphate in the management of PSA progression following primary androgen deprivation for metastatic prostate cancer

Abstract

4668 Background: Although the majority of patients with metastatic prostate cancer (PCA) initially respond to androgen deprivation, most will ultimately fail. Currently, no standard therapy exists for these patients and second-line hormonal therapy with estramustinphosphat (EMP) or ketokonazol/hydrocortisone (KHC) has been described to produce response rates of 30 to 60%. It was the purpose of this prospective randomized phase-II trial to compare clinical efficacy and side effects of both regimens. Methods: To become eligible for the study, patients had to show (1) PSA-progression at 2 consecutive measurements 2 weeks apart, (2) PSA progression following antiandrogen withdrawal and castration levels of testosterone. In 35 patients, EMP was applied at 300 - 350 mg/die intravenously on 7 consecutive days followed by oral medication with 3x 280 mg/day until PSA progression. In 30 patients, K consisted of 800 mg/day and replacement HC at 30 mg/day until PSA progression. On the EMP and KHC group, 10 and 6 patients underwent antiandrogen withdrawal, all other patients had received LHRH therapy or orchiectomy. Primary endpoint was PSA response; PSA was measured at 6 weeks intervalls, treatment associated side effects were documented. Results: Of 35 patients in the EMP group, 8 (23%) demonstrated a PSA decrease > 50% with a median duration of 3 (2–12) months. Of 30 patients in the KHC group, 18 (61%) patients exhibited a PSA decrease > 50% with a median duration of 7.5 (3–34) months. Response rates were higher in patients with LHRH or orchiectomy as compared to patients with PSA progression following antiandrogen withdrawal. Differences in PSA response and response duration were statistically significant. In the EMP group, 12 (34%) patients discontinued therapy due to significant side effects; 3 (9%) patients developed deep venous thrombosis. In the KHC group, no WHO grade III/IV side effects were observed, none of the patients discontinued treatment. Conclusions: KHC appears to be an effective therapeutic approach in patients with hormone-sensitive PCA after primary androgen deprivation. EMP, however, is a toxic regimen with minimal therapeutic response. No significant financial relationships to disclose.