Multicentre study on the efficacy and tolerability of an extract of Serenoa repens in patients with chronic benign prostate conditions associated with inflammation.

INTRODUCTION: Chronic benign prostate diseases are very common and certainly feature significantly in urological practice.The treatment of chronic benign prostate diseases is a common problem in clinical practice: few studies have been conducted in routine clinical practice to evaluate the efficacy of the treatments for this clinical condition. The objective of this study was to evaluate the efficacy of an extract of Serenoa repens (Permixon) in the treatment of lower urinary tract symptoms (LUTS) in patients with chronic benign prostate diseases with associated inflammation, also taking into consideration the influence of treatment on sexual function and, therefore, on patients' quality of life. MATERIALS AND METHODS: All the 591 eligible subjects were evaluated on entering the study; after a screening visit, including medical history, physical examination, physical examination and digital rectal examination (DRE) and laboratory tests, the patients underwent uroflowmetry. The subjects under investigation were also asked to complete the IPSS, NIH-CPSI and IIEF-5 questionnaires, for the purpose of evaluating urinary symptoms and erectile function in relation to sexual activity in the previous 6 months. RESULTS: The analysis of the uroflowmetry results showed that treatment with extract of Serenoa repens distinctly improves bladder voiding and lower urinary tract symptoms, as highlighted also by the improvement in the scores for the IPSS and NIH-CPSI questionnaires which serve as a basis for evaluating the urinary symptoms of patients with prostatic hyperplasia and chronic prostatitis respectively. The results also suggest that using an extract of Serenoa repens for 6 months in patients with chronic benign prostate diseases gives rise to an improvement in erectile function, as demonstrated by the increase in the scores for the IIEF-5 questionnaire after 6 months of treatment. CONCLUSIONS: The results of this study demonstrate how treatment for 6 months with an extract of Serenoa repens in routine clinical practice gives rise to a statistically significant improvement in Qmax values and in the IPSS, NHI-CPSI and IIEF-5 questionnaire scores, resulting not only in an improvement in urinary symptoms but also in an overall improvement in patients' quality of life.

BAG3 protein delocalisation in prostate carcinoma.

Despite the progressive increase of early diagnosis, a subset of prostate cancers show a metastasizing and lethal course, not always predictable upon the traditional prognostic parameters. The object of this study was to investigate the role of the survival co-chaperone protein BAG3 as a new prognostic marker for prostate cancer. BAG3 was detected by immunohistochemistry in 55 specimens of surgically removed prostate carcinomas and in 15 surgical specimens of non-neoplastic prostate tissues. Results were compared with clinic-pathological data and outcome of patients and statistically evaluated. BAG3 resulted expressed in all the cases: Non-neoplastic prostate tissue showed a cytoplasmatic staining with apical reinforcement, a finding which appears consistent with the reported connection of the protein with the membrane focal cell-adhesion complexes. In prostate carcinomas, BAG3 showed a progressive decrease of the expression level from well- to low-differentiated carcinoma, coupled with the loss of polarisation of the signal in metastasizing cases. These results indicate that BAG3 intra-cytoplasmic delocalisation is a specific feature of cancer versus non-neoplastic prostate and a candidate new marker for prediction of prostate cancer invasiveness and behaviour.

Phase 1/2 study of intravenous paclitaxel and oral cyclophosphamide in pretreated metastatic urothelial bladder cancer patients.

BACKGROUND: To the authors' knowledge, no previous studies have been reported with the combination of paclitaxel and oral cyclophosphamide in patients with metastatic bladder cancer. A phase 1/2 study was conducted of paclitaxel in combination with oral cyclophosphamide for patients with advanced urothelial bladder cancer who had been previously treated with gemcitabine/cisplatin chemotherapy as first-line metastatic treatment. METHODS: This was a single-arm phase 1/2 study. Patients were treated with paclitaxel and oral cyclophosphamide at 3-week intervals until disease progression or irreversible toxicity occurred. Primary endpoints were to determine the maximum tolerated doses (MTD) and objective response rate; secondary endpoints were safety, time to disease progression (TTP), and overall survival (OS). RESULTS: Forty-four patients were enrolled. Dose levels of paclitaxel of 175 mg/m(2) (Day 1) and cyclophosphamide of 50 mg (Days 1-7 orally) (dose level I) of a 21-day cycle were tolerated without dose-limiting toxicities (DLTs). At a cyclophosphamide dose of 100 mg (dose level II) the MTD was exceeded; 3 of 6 patients experienced a DLT (grade 3 constipation and grade 4 neutropenia and thrombocytopenia [toxicities were graded using National Cancer Institute Common Toxicity Criteria (version 3.0)]). Dose level I was expanded and determined to be the MTD. A total of 32 patients were treated at dose level I in the phase 2 portion. Partial responses were observed in 31% of patients (10 of 32 patients; 95% confidence interval [95% CI], 17%-45%). Grade 1/2 vomiting, peripheral neuropathy, and neutropenia were the most common side effects, noted in 11 (34%), 8 (25%), and 10 (31%) patients, respectively. The median TTP was 5 months (95% CI, 2 months-7.5 months) and the median OS was 8 months (95% CI, 4 months-14 months). CONCLUSIONS: The combination of paclitaxel and cyclophosphamide is well tolerated and associated with promising efficacy. Further trials are needed to confirm these preliminary results.

Phase II trial of gemcitabine, prednisone, and zoledronic acid in pretreated patients with hormone refractory prostate cancer.

OBJECTIVES: To investigate the impact on biochemical and objective response and on pain improvement of gemcitabine, prednisone, and zoledronic acid in patients with hormone-refractory prostate cancer (HRPC), previously treated with docetaxel-based regimens. METHODS: The patients were treated with gemcitabine 1000 mg/m2 every 14 days, prednisone 10 mg orally on days 1 to 7 and 14 to 21, and zoledronic acid every 4 weeks. Changes in prostate-specific antigen levels, tumor response, and toxicity were evaluated every month. The pain response, based on pain reduction and analgesic drug reduction, was assessed during therapy. RESULTS: A total of 22 men (median age 65 years) were treated. Overall, 5 patients (23%) achieved a 50% or greater reduction in prostate-specific antigen level after two cycles; a partial response was observed in 1 (14%) of 7 patients with measurable disease, and 3 (43%) of 7 had stable disease. Of the 22 men, 23% had pain improvement. The most important hematologic toxicity was neutropenia (grade 3 in 18%). CONCLUSIONS: The combination of gemcitabine, prednisone, and zoledronic acid appears to be associated with biochemical response, pain improvement, and good safety in pretreated patients with HRPC.