15636 Background: The present multi-centre phase II study was designed to support the hypothesis that networking agents binding to ubiquitous accessible targets in metastatic hormone-refractory prostate cancer (HRPC) may counteract neoplasia-specific aberrant cellular functions, thereby mediating objective response (primary endpoint). Method: Patients with metastatic HRPC, received both an anti- inflammatory and angiostatic therapy consisting of low-dose chemotherapy with capecitabine 1 g twice daily for 14 days every 3 weeks, day 15+, COX-2 blockade with etoricoxib 60 mg daily, day 1+, combined with two transcription modulators, pioglitazone 60 mg daily, day 1+, plus dexamethason 1 mg daily for 14 days, every 3 weeks, day 15+, until disease progression. The study was planned using the Simon optimal design. Results: Thirty-six consecutive patients (N= 22 (61%) chemo-naive, n= 14 (39%) with preceding chemotherapies, mean 2.1 regimen) with metastatic HRPC, confirmed PSA increase, assessable response, and ECOG 0–2 were enrolled between 1/03 to 5/06. Objective response occurred in 10 of 13 cases (N/n: 41%/7%) with PSA (and C-reactive protein) response >50% (N/n: 45%/21%). Median time to PSA response was 2.4 months (range 1.0 to 7.3 months). Two of three patients responding with PSA <4 ng/ml achieved complete remission after 9 and 16 months, 16 patients stable disease (N/n: 41%/64%), and 5 patients experienced progressive disease (N/n: 14%/14%). Median progression-free survival (PFS) was 3.6 months (range 0.5 to 28.5) and median overall survival (OS) 14.4 months (range 0.6 to 37.2). Multivariate analysis recognized pre-treatment with chemotherapy as negative predictor for both OS (hazard ratio 2.26 (CI 95%: 0.970; 5.277), p=0.05) and PFS (HR 2.47 (CI 95%: 1.146; 5.348), p= 0.02), and <50% PSA response as negative predictor for PFS (HR 0.38 (CI 95%: 0.171; 0.857), p= 0.01). Toxicities > WHO grade II were reported: Hand-foot syndrome (n=1), anemia (n=6), edema (n=1), cushing syndrome (n=1), hydronephrosis (n=1). Conclusions: This is the first study reporting continuous complete remissions in HRPC with a biomodulatory therapy approach. Further, the study may clinically support the upper mentioned hypothesis. No significant financial relationships to disclose.
IFN-γ sensitization of prostate cancer cells to fas-mediated death: a gene therapy approach
