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: To prospectively study the pharmacokinetics and toxicity profile of docetaxel in elderly patients with cancer. Docetaxel was administered at a dose 75 mg/m(2) once every 3 weeks to 25 elderly cancer patients aged >/= 65 years and 26 cancer patients aged younger than 65 years. Pharmacokinetic studies and toxicity assessments were performed during the first cycle of therapy. Of 51 patients treated, 20 aged >/= 65 years (median, 71 years; range, 65 to 80 years) and 20 aged younger than 65 years (median, 53 years; range, 26 to 64 years) were assessable for pharmacokinetic studies, and 39 were assessable for toxicity. Patient characteristics were similar (P >/= .15) between the two cohorts. Mean docetaxel clearance was not altered in the elderly versus younger patients: 30.1 L/h (standard deviation [SD] 18.3 L/h) v 30.0 L/h (SD, 14.8 L/h; P = .98). The percentage of patients with grade 4 and febrile neutropenia was higher in the elderly (63% and 16%, respectively) versus younger (30% and 0%, respectively) cohort, although this observation did not reach a level of statistical significance (P = .056). From logistic regression analysis, the odds ratio for a patient aged 65 years was 1.98 for developing grade 4 neutropenia compared with a patient aged 50 years (P = .091). Docetaxel plasma pharmacokinetics are unaltered in elderly patients. Patients aged >/= 65 years appear to be more sensitive to docetaxel-induced neutropenia.Journal of Clinical Oncology 02/2005; 23(6):1070-7. · 18.04 Impact Factor
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ABSTRACT: The TAX 327 study compared 3-weekly docetaxel, weekly docetaxel or 3-weekly mitoxantrone, each with prednisone, for 1006 patients with metastatic hormone-refractory prostate cancer. Survival and symptom control were superior following 3-weekly docetaxel as compared with mitoxantrone. At progression, many patients were treated with the other drug. Here, we provide a retrospective report of survival and prostate-specific antigen (PSA) response after second-line therapy. The TAX 327 database provided information about treatment after progression on first-line therapy, and survival has been updated. Investigators were asked to provide information about crossover treatment and serial PSA values. We identified 232 crossover patients. Median survival after crossover was 10 months and did not depend on direction of crossover. Data on PSA response are available for 96 patients: PSA response (> or =50% reduction) occurred in 15% of 71 men receiving mitoxantrone after docetaxel and in 28% of 25 men receiving docetaxel after mitoxantrone. Median PSA progression-free survival was 3.4 months for mitoxantrone after docetaxel and 5.9 months for docetaxel after mitoxantrone. One quarter of men received crossover therapy and survival was similar in the crossover groups. The PSA response rate to docetaxel after mitoxantrone was higher than that for mitoxantrone after docetaxel.Annals of Oncology 05/2008; 19(10):1749-53. · 7.38 Impact Factor
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ABSTRACT: To evaluate the efficacy and toxicity of docetaxel plus prednisolone treatment in Japanese patients with hormone-refractory prostate cancer (HRPC). From April 2004 through August 2008, we used docetaxel plus prednisolone to treat 55 HRPC patients (median age, 72 years). Eighteen patients (32.7%) had measurable soft tissue lesions, whereas 52 patients (94.5%) had bone metastases. During the 21-day treatment cycle, docetaxel (70 mg/m(2)) was administered once every 21 days and oral prednisolone (5 mg), twice daily. Prostate-specific antigen (PSA) response, defined as a reduction of at least 50% in the baseline levels for 4 weeks, was evaluated. The median follow-up period was 30.1 months; median overall survival, 15.3 months and median progression-free survival, 7.5 months. During follow-up, 37 patients (67.3%) achieved the PSA response, and 5 of 18 (27.8%) patients with measurable disease showed a partial response. Among the 27 patients who experienced cancer pain before treatment initiation, 15 (55.5%) reduced their analgesic drug intake. Multivariate analysis of the prognostic variables revealed a significant association between the overall survival and pain (P = 0.033). Hematological toxicity (grades 3-4) included neutropenia (87.3%), febrile neutropenia (25.5%) and thrombocytopenia (5.5%). Frequent non-hematological adverse events were general edema (52.7%), general fatigue (32.7%) and sensory neuropathy (30.9%). Three patients died of adult respiratory distress syndrome (ARDS). Docetaxel plus prednisolone treatment is effective in Japanese HRPC patients. The main toxicity is neutropenia, which can be safely controlled by outpatient treatment with granulocyte-colony stimulating factor. However, the Japanese patients in our study developed ARDS more frequently than other patients in previous studies did.Japanese Journal of Clinical Oncology 11/2010; 40(11):1092-8. · 1.90 Impact Factor