Biomodulatory Treatment of Patients with Castration-Resistant Prostate Cancer: A Phase II Study of Imatinib with Pioglitazone, Etoricoxib, Dexamethasone and Low-Dose Treosulfan

作者：Martin Vogelhuber, Susan Feyerabend, Arnulf Stenzl, T. Suedhoff, Matthias B. Schulze, Jutta Huebner, R. Oberneder, W.F. Wieland, Stefan C. Mueller, Florian Eichhorn, Hans Heinzer, Katja Schmidt, Monika Baier, A. Ruebel, Katrin Birkholz, A. Bakhshandeh-Bath, Reinhard Andreesen, W. Herr, Albrecht Reichle · 发表于：Cancer Microenvironment · 年份：2014 · DOI：10.1007/s12307-014-0161-7 · 被引用次数：14 · 研究领域：Prostate Cancer Treatment and Research、Multiple Myeloma Research and Treatments、Peptidase Inhibition and Analysis

Therapeutic options for patients with castration-resistant prostate cancer (CRPC) remain limited. In a multicenter, Phase II study, 65 patients with histologically confirmed CRPC received a biomodulatory regimen during the six-month core study. Treatment comprised daily doses of imatinib mesylate, pioglitazone, etoricoxib, treosulfan and dexamethasone. The primary endpoint was prostate-specific antigen (PSA) response. Responders could enter an extension phase until disease progression or intolerable toxicity occurred. Mean PSA was 45.3 ng/mL at baseline, and 77 % of patients had a PSA doubling time <3 months. Of the 61 evaluable patients, 37 patients (60.6 %) responded or had stable disease and 23 of them (37.7 % of 61 patients) were PSA responders. Among the 23 responders mean PSA decreased from 278.9 ± 784.1 ng/mL at baseline to 8.8 ± 11.6 ng/mL at the final visit (week 24). The progression-free survival (PFS) was 467 days in the ITT population. Of the 947 adverse events, 57.6 % were suspected to be drug-related, 13.8 % led to dose adjustment or permanent discontinuation and 40.2 % required concomitant medication. This novel combination approach led to an impressive PSA response rate of 37.7 % in CRPC patients. The good PSA response and PFS rate combined with the manageable toxicity profile suggest an alternative treatment option.