T. Nelius

A randomized study of docetaxel and dexamethasone with low‐ or high‐dose estramustine for patients with advanced hormone‐refractory prostate cancer

To test the combination of docetaxel with two different doses of estramustine in patients with hormone‐refractory prostate cancer (HRPC), to improve response rates and to lower side‐effects, as docetaxel‐based chemotherapy is an increasing option for men with advanced HRPC, and alone or combined with estramustine, docetaxel improves median survival.

Pigment epithelium-derived factor expression prolongs survival and enhances the cytotoxicity of low-dose chemotherapy in castration-refractory prostate cancer

There is currently no cure for advanced castration-refractory prostate cancer (CRPC) despite the recent approval of several new therapeutic agents. We report here the anti-tumor effect of the angio-inhibitory pigment epithelium-derived factor (PEDF) in the metastatic LNCaP-derivative CRPC CL1 model and explore PEDF anti-neoplasic efficacy in combination with low-dose chemotherapy. Androgen-sensitive LNCaP and CRPC PC3 cell lines were examined as comparison. Using a retroviral expression system, we showed that PEDF limited the proliferation of all prostatic cell lines tested; an effect attributed to interleukin 8 (IL8)-CXCR1/IL8RA inhibition. PEDF also reduced the number and size of 3D tumor spheroids in vitro, but only induced cell differentiation in CRPC spheroids. Similarly, PEDF inhibited the migration of CRPC cells suggesting both anti-proliferative and anti-migratory functions. In vivo, PEDF decreased by 85% and 65% the growth of subcutaneous (s.c.) PC3 and CL1 tumors, respectively. In the CL1 orthotopic model, tumor intake with lethal metastases was found in all animals; nevertheless, PEDF prolonged the median survival of tumor-bearing mice (95% confidence interval: 53±0.001 to 57±1 days). Accordingly, PEDF delayed the emergence of skeletal-related event in intra-tibial xenografts. Next, we evaluated low-dose docetaxel (DTX; 5, 1, 0.5u2009mg/kg) or cyclophosphamide (CTX; 10–20u2009mg/kg) on established s.c. PC3 tumors that conditionally express PEDF anti-tumoral epitope/NT3. Although NT3–DTX-5u2009mg/kg combination was inefficient, NT3–DTX-1u2009mg/kg and -0.5u2009mg/kg inhibited by 95% and 87.8%, respectively, tumor growth compared with control and induced tumor stasis. Both NT3–CTX combinations were advantageous. Inversely, PEDF–DTX-5u2009mg/kg and PEDF–CTX-10u2009mg/kg delayed the most CL1 tumor growth (15, 11 and 5 days for PEDF–DTX-5u2009mg/kg, PEDF–CTX-10u2009mg/kg and single treatments, respectively) with elevated apoptosis and serum thrombospondin-1u2009as possible mechanism and marker, respectively. As well, both PEDF–CTX-10u2009mg/kg and PEDF–DTX-5u2009mg/kg prolonged significantly the survival of tumor-bearing mice compared with single treatments. Metastases were reduced in PEDF–DTX-5u2009mg/kg compared with other treatments, suggesting that PEDF–DTX delayed metastases formation. Our results advocate that PEDF/low-dose chemotherapy may represent a new therapeutic alternative for CRPC.

Characterization of Prognostic Factors and Efficacy in a Phase-II Study with Docetaxel and Estramustine for Advanced Hormone Refractory Prostate Cancer

Background: Docetaxel based chemotherapy not only reduces pain and improves quality of life in advanced hormone refractory prostate cancer (HRPC), but it also improves survival. We investigated the combination of docetaxel and estramustine in patients with HRPC regarding efficacy and prognostic parameters. Patients and Methods: We conducted a phase-II trial, administering docetaxel (70 mg/m2 i.v., day 2, every 3 weeks) and estramustine (280 mg 3 times daily p.o., 1 day prior to docetaxel, on 5 consecutive days) to patients with HRPC. Patients were monitored for PSA (prostate-specific antigen) response and toxicity. Results: 62 patients were treated. The median age was 67.5 years, the median PSA was 177.9 ng/ml. The median number of cycles was 6. The median time to progression (TTP) and median survival time were 14 (±2) and 24 (±5) months, respectively. A = 50% decrease in PSA levels from baseline occurred in 38 (61.3%) patients of whom 25 (40.3%) had a = 75% PSA decrease. The main grade 3-4 hematologic toxicities were neutropenia 34% and anemia 18%. Conclusions: The combination of docetaxel and estramustine exerts substantial activity in HRPC suggesting an overall survival benefit with manageable toxicity. This trial also demonstrated a survival advantage for patients with early chemotherapeutic intervention. We identified PSA relapse, baseline PSA and hemoglobin as valuable prognostic factors in this setting.

Docetaxel (D) plus estramustine monophosphate (EMP) in patients (pts) with hormone refractory prostate cancer (HRPC)

4780 Background: D mono therapy has proven efficacy in pts with HRPC, but combination of D/EMP has improved response rates do to synergistic and significant activity. However, the optimal dose and ...

Laparoscopic (endoscopic) radical prostatectomy: techniques and results

Laparoscopic radical prostatectomy (LRP) is a relatively new technique for treating organ-confined prostate cancer. Recent progress of laparoscopic/endoscopic techniques allow to perform these complex oncological procedure. Since the first description of LRP in the early 1990s the technique has undergone significant technical modifications. Two operation routes were mainly used: the transperitoneal LRP and the extraperitoneal endoscopic radical prostatectomy (EERPE). Here we review the surgical techniques of both operation routes, and highlight results, outcome and complications. The transperitoneal LRP and the EERPE can be used successfully and reproducibly, giving results comparable with those from the open retropubic procedure. Despite many advantages, transperitoneal LRP is associated with potential intraperitoneal complications. The technical improvements of the EERPE completely obviates these complications. The available data are encouraging and promising, but long-term oncological results will define the definitive role of these new techniques. We truly believe that minimally invasive surgery in treating localized prostate cancer has a bright future and that these techniques will continue to be developed.