Weekly low-dose docetaxel combined with estramustine and dexamethasone for Japanese patients with metastatic castration-resistant prostate cancer

Department of Urology, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, 565-0871, Japan.
International Journal of Clinical Oncology (Impact Factor: 2.13). 06/2012; 18(4). DOI: 10.1007/s10147-012-0429-1
Source: PubMed


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).

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.

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.

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/m(2) every 3 weeks) (standard-dose group), and 76 CRPC patients were treated with weekly low-dose DTX (20-30 mg/m(2) 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.
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    ABSTRACT: The aim of this study was to determine the correlation between PSA response rate (PSA RR) and overall survival (OS) and identify PSA RR as a potential surrogate for OS, in docetaxel-based first-line treatments for castration-resistant prostate cancer (CRPC). Trials of first-line regimens with docetaxel for patients with metastatic CRCP published between 2004 and 2013 were identified, and data were evaluated statistically in order to investigate the correlation between PSA RR and OS. A total of 22 trials were identified and included in our analysis, for a total of 7,677 patients. In addition, we divided all the trails and arms of the randomized trials in two subgroups, the first one composed only of docetaxel (D) plus prednisone (P) regimens (standard therapy) and the second one composed of all D + other drug combinations (D combinations). Analysing all the trials and arms as a single unit, we found a statistically significant correlation between PSA RR and OS, with Spearman's rank correlation coefficient ρ = 0.50 (95 % confidence interval (CI), 0.47 to 0.88) (P = 0.003). Also evaluating the standard therapy group, we found a statistically significant correlation between PSA RR and OS, with Spearman's ρ = 0.65 (95 % CI, 0.38 to 0.70) (P = 0.02). However, when we assessed the D combination group, we found Spearman's rank correlation coefficient decreased (ρ = 0.42) (95 % CI, 0.28 to 0.80) and resulted nonstatistically significant (P = 0.06). In conclusion, we found a statistically significant correlation between PSA RR and OS. The usage of PSA RR as a surrogate marker for OS in metastatic CRPC patients treated with D-based first-line regimens may be appropriate only in the D + P combination.
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