Weekly low-dose docetaxel combined with estramustine and dexamethasone for Japanese patients with metastatic castration-resistant prostate cancer
ABSTRACT BACKGROUND: A low-dose chemotherapy consisting of docetaxel, estramustine and dexamethasone was investigated for its beneficial effect and feasibility in Japanese patients with metastatic castration-resistant prostate cancer (CRPC). METHODS: Seventy-two Japanese patients with metastatic CRPC were enrolled to receive docetaxel (25 mg/m(2) on days 2 and 9), estramustine phosphate (280 mg orally twice daily from day 1 to day 3 and from day 8 to day 10) and dexamethasone (0.5 mg orally twice daily) every 21 days. RESULTS: The median age of the patients was 72 years and 64 patients (89 %) had ≥grade 1 anemia at entry. The median total number of courses administered was 8.5 (range 1-93). Forty-two patients (58 %) had a prostate-specific antigen (PSA) decline of ≥50 %. The median progression-free survival and overall survival were 6 and 23 months, respectively. Fifteen patients (21 %) improved and 53 patients (74 %) were stable in their performance status. Of the 40 patients with bone pain, 25 patients (63 %) showed pain reduction. Among 71 patients assessable for their hemoglobin levels, 21 patients (30 %) achieved an increase of at least 1.0 g/dl. Of the 5 patients who terminated treatment because of ≥grade 3 toxicity, 4 patients had pneumonitis and one patient had anemia. Only one patient developed ≥grade 3 neutropenia. CONCLUSIONS: The low-dose combination of docetaxel, estramustine and dexamethasone is active and tolerable with beneficial effects on serum PSA levels, performance status, anemia and bone pain in Japanese patients with CRPC. This regimen is a reasonable option for elderly patients with bone disease at risk of hematologic toxicity.
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ABSTRACT: BACKGROUND: We retrospectively investigated the efficacy and safety profile of weekly low-dose docetaxel (DTX) with estramustine in comparison with triweekly standard-dose DTX treatment for Japanese patients with castration-resistant prostate cancer (CRPC). METHODS: Between April 2002 and January 2011, 75 CRPC patients were treated with triweekly DTX (60-75 mg/m2 every 3 weeks) (standard-dose group), and 76 CRPC patients were treated with weekly low-dose DTX (20-30 mg/m2 on days 2 and 9 with estramustine 560 mg on days 1-3 and 8-10) every 3 weeks (low-dose group). Prostate-specific antigen (PSA) response and progression-free and overall survival were analyzed in each group. RESULTS: Median serum PSA level of the standard-dose group and low-dose group was 25.0 and 35.5 ng/ml, respectively. In the standard-dose and low-dose groups, 57.8 and 65.2 % of patients, respectively, achieved a PSA decline ≥50 %. There was no significant difference in either median time to progression between the standard-dose group (10.0 months) and low-dose group (7.1 months) or in median duration of survival between the standard-dose group (24.2 months) and low-dose group (30.6 months). Multivariate analysis with a Cox proportional hazards regression model showed that DTX treatment protocol did not influence the risk of death. Incidences of grade 3-4 neutropenia, febrile neutropenia, and thrombocytopenia were significantly higher in the standard-dose versus low-dose group (58.7 vs. 7.9 %, 16.0 vs. 3.9 %, and 8.0 vs. 0 %, respectively). CONCLUSION: For Japanese CRPC patients, weekly low-dose DTX combined with estramustine has similar efficacy to standard-dose DTX but with fewer adverse events.International Journal of Clinical Oncology 03/2013; 19(1). DOI:10.1007/s10147-013-0536-7 · 2.17 Impact Factor
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ABSTRACT: The tremendous research effort on diseases and drug discovery has produced a huge amount of important biomedical information which is mostly hidden in the web. In addition, many databases have been created for the purpose of storing enormous amounts of information and high-throughput experiments related to drugs and diseases' effects on genes. Thus, developing an algorithm to integrate biological data from different sources forms one of the greatest challenges in the field of computational biology. Based on our belief that data integration would result in better understanding for the drug mode of action or the disease pathophysiology, we have developed a novel paradigm to integrate data from three major sources in order to predict novel therapeutic drug indications. Microarray data, biomedical text mining data, and gene interaction data have been all integrated to predict ranked lists of genes based on their relevance to a particular drug or disease molecular action. These ranked lists of genes have finally been used as a raw material for building a disease–drug connectivity map based on the enrichment between the up/down tags of a particular disease signature and the ranked lists of drugs. Using this paradigm, we have reported 13% sensitivity improvement in comparison with using microarray or text mining data independently. In addition, our paradigm is able to predict many clinically validated disease–drug associations that could not be captured using microarray or text mining data independently.Journal of Bioinformatics and Computational Biology 03/2014; DOI:10.1142/S0219720014500073 · 0.93 Impact Factor