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Objective To analyze prognosic factors for patients with hormone refractory prostate cancer (HRPC) after chemotherapy of docetaxel/mitoxantrone plus prednisone and to explore the relationship between prostate specific antigen (PSA) parameters and prognosis. Methods Data from 68 patients with CRPC after chemotherapy were collected and analyzed retrospectively.The median age of these patients were 65 years old with 28 cases of biopsy Gleason score ＜ 8 and 35 cases of ≥ 8.The median serum PSA at diagnosis,nadir and pre-chemotherapy baseline were 142 ng/ml,0.5 ng/ml and 33.0 ng/ml,respectively.There were 38 patients in docetaxel group and 30 in mitoxantrone group.PSA doubling time ( PSADT),progression free survival (PFS) and overall survival (OS) was calculated.Chi square test was used in analysis of chemotherapy effect and Cox proportional hazards regression model was applied to identify the predictors for PFS and OS.The median value of continuous variable as cutoff point was used to divide patients into two groups to compare.Risk ratio and 95％ confidence interval (CI) was calculated. Results 38 (55.9％)patients experienced effective chemotherapy. The effective rate were 33％ and 74％ for PSADT ＜ 1.6 months and ≥ 1.6 months group,85％ and 49％ for M0 and M1 stage group,and 69％ and 40％ for docetaxel and mitoxantrone group,(P ＜ 0.05).The median PFS was (3.5 ± 0.5) months for all patients,which were (2.7 ±0.4) months and (5.9 ±0.6) months for patients with PSADT ＜ 1.6 months and ≥ 1.6 months group,(5.0 ± 0.6) months and (2.7 ± 0.5 ) months for patients with docetaxel and mitoxantrone group,and (5.7 ± 0.8) months and ( 3.4 ± 0.6) months for patients with Gleason score ＜ 8 and ≥ 8 group (P ＜0.05).26 case died in the end and the median OS was (28.3 ± 2.6) months for these patients,which were (15.7 ± 3.4) months and (31.6 ± 1.2) months for patients with PSADT ＜ 1.6 months and ≥1.6 months group,(29 ± 4.1 ) months and (28 ± 3.2) months for patients with docetaxel and mitoxantrone group,and (28.7 ± 2.6) months and (24.3 ± 5.6) months for patients with Gleason score ＜ 8 and ≥ 8 group (P ＜ 0.05). Conclusions The effective rate of chemotherapy was related with PSADT,chemotherapy strategy and M stage.PSADT,chemotherapy strategy and Gleason score may be independent predictors for patients with HRPC taking chemotherapy.Patients with PSADT ≥ 1.6 months,docetaxel chemotherapy and Gleason score ＜ 8 will have longer PFS and OS.
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PURPOSE: To assess the efficacy and safety of treating Korean patients with metastatic hormone-refractory prostate cancer (HRPC) using docetaxel plus prednisolone chemotherapy. MATERIALS AND METHODS: This was a retrospective cohort study performed in 98 patients with metastatic HRPC between October 2003 and April 2008. After screening, 72 patients fit the eligibility criteria for inclusion in this study. Treatment consisted of 5 mg prednisolone twice daily and 75 mg/m2 docetaxel once every 3 weeks. RESULTS: Patient demographic characteristics included: median age 67 years (range, 51~86), median ECOG performance status 1 (0~2), Gleason score > or =8 in 61 patients (86%), and median serum PSA 45.5 ng/mL (range, 3.7~2,420.0). A total of 405 cycles of treatment were administered with a median 6 cycles (range, 1~20) per patient. The median docetaxel dose-intensity was 24.4 mg/m2/week (range, 17.5~25.6). A PSA response was seen in 51% of 63 evaluable patients at 12 weeks and maximal PSA decline > or =50% in 59% of 70 evaluable patients. Tumor response was evaluated in 13 patients, 4 patients achieved PR, and 5 patients had SD with a response rate of 31%. With a median follow-up duration of 23.1 months (95%CI, 16.7~29.5), the median time to PSA progression was 5.1 months (95%CI, 4.5~5.8) and median overall survival was 22.8 months (95%CI, 16.6~29.1). Nine (13%) patients experienced grade 3 or higher febrile neutropenia. CONCLUSION: This chemotherapy regimen (docetaxel every 3 weeks plus prednisolone daily) demonstrated a strong response in Korean patients with metastatic HRPC, while the toxicity profile was manageable and similar to that observed in Western patients.
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Humans , Cohort Studies , Follow-Up Studies , Korea , Mass Screening , Neoplasm Grading , Neutropenia , Prednisolone , Prostate , Prostatic Neoplasms , Retrospective Studies , TaxoidsABSTRACT
PURPOSE: We wanted to evaluate the efficacy and toxicity of the newly developed oral glyceryl monooleate (GMO)-paclitaxel in a hormone refractory prostate cancer model. MATERIALS AND METHODS: A paclitaxel formulation was prepared from GMO, tricaprylin, Tween(R) 80 and paclitaxel. The tumor cells of prostate cancer (DU-145 cells) were incubated and then put into different paclitaxel concentrations. The tumoricidal activity was measured by using an indirect methylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT) assay. Cells of the DU-145 cell line were subcutaneously heterotransplanted into 18 nude mice, and they developed prostate cancer. The 18 mice were divided into 3 groups; the control group was injected with the DU-145 cell line (n=6), the GMO group was injected with GMO after the DU-145 cells were injected (n=6), and the oral GMO-paclitaxel group was injected with oral GMO-paclitaxel after the DU-145 cells were injected (n=6). The tumor volume was measured every week and the main organs were evaluated pathologically to determine the toxicity. RESULTS: On the MTT assay, the control group and the GMO group did not display cytotoxicity. However, treatment with the various GMO-paclitaxel formulations (0.1 microgram/ml, 1 microgram/ml, 10 microgram/ml) for treating the DU-145 cell line cancer induced cytotoxicity in a dose dependent fashion. The tumor volumes were not significantly changed in the group that was administered oral GMO-paclitaxel. However, there were significantly increased tumor volumes in the control group and the GMO group (p<0.05). Toxic changes were not detected in liver and kidney, and there was normal cellularity with a normal myeloid:erythroid ratio in the mice after the administration of oral GMO-paclitaxel. CONCLUSIONS: The newly developed oral GMO-paclitaxel has a remarkable cytotoxic effect against DU-145 cells without systemic toxicity. Therefore, oral GMO-paclitaxel therapy promises to be a safe and effective modality for treating hormone refractory prostate cancer, and it can possibly replace IV paclitaxel.
Subject(s)
Animals , Mice , Cell Line , Kidney , Liver , Mice, Nude , Paclitaxel , Prostate , Prostatic Neoplasms , Tumor BurdenABSTRACT
Treatment of hormonal refractory prostate cancer (HRPC) is nowadays a challenge in the clinic. Although different types of treatment such as chemotherapy, radiotherapy, biotherapy, and radioisotope treatment have been used, their effects on patients' survival is uncertain. Docetaxel plus prednisone has been confirmed to be the first line regimen, which can effectively increase patients' survival. Zoladronic acid has been demonstrated to be efficacious in reducing bone related events, and has been widely applied in bone metastasis of prostate cancer. Targeted therapy is currently under intensive investigation for HRPC treatment, and many early clinical studies have shown their effective results, and further studies with larger samples may prove their efficacy. This review will cover different topics in terms of the treatment of hormonal refractory prostate cancer and update the progresses in recent clinical trials.
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Background and purpose:Chemotherapy with docetaxel has become the first line treatment for hormone refractory prostate cancer.To preliminarily investigate the efficacy of docetaxel plus prednisone and mitoxantrone plus prednisone for treating metastatic hormone-refractory prostate cancer and to further evaluate its adverse events in Chinese patients. Methods:83 patients with metastatic hormone-refractory prostate cancer were candidates for the trial and given a combination of docetaxel 75 mg/m2 intravenously on d 1 or mitoxantrone 12 mg/m2 on day 1 plus prednisone 5 mg twice daily on d 1~21, 21 days a cycle. Serum PSA level, relief of bone pain, myelosuppression, and vomiting were recorded and calculated.Results:Docetaxel plus prednisone were administered to 44 patients, 13.6% (6/44) of them got a complete response; 29.5% (13/44) achieved a partial response; 29.5% (13/44) had stable disease; and 27.3% (12/44) progressed. The average time to PSA progression was 37.8 weeks (12~101 weeks) in the responsive and stable disease patients. The 12 patients with progressive disease were given MP as a salvage therapy, and 16.7% (2/12) achieved a partial response, 25.0% (3/12) had stable disease. Only 2 patients died of disease aggravation. Mitoxantrone plus prednisone were given to 39 patients, and 7.7% (3/39) of them got a complete response; 25.6% (10/39) achieved a partial response; 25.6% (10/39) had a stable disease; and 41.0% (16/39) of patients progressed. The mean time to PSA progression was 25.3 weeks (8~61 weeks) in the responsive and stable disease patients. The 14 patients with progressive disease were administered DP as a salvage therapy, and 7.1% (1/14) achieved a complete response, 35.7% (5/14) got a partial response, 21.4% (3/14) had stable disease and from the new baseline. Four patients died at the last follow-up.Conclusions:In Chinese patients, docetaxel plus prednisone is better than mitoxantrone plus prednisone in PSA response rate and PSA control, but there occurs a bit more toxicity. When the tumor is resistant to one regimen, the other might be still effective in controlling the disease from progression.
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Objective To evaluate the efficacy of oral etopside (VP16) and oral cyclophosphamide (CPM) combination in the treatment of hormone-refractory prostate cancer (HRPC). Methods Between June 2000 and July 2003,9 patients with HRPC were treated with oral etopside (50 mg/d) and oral cyclophosphamide (100 mg/d) for 21 days with every 28 days as a cycle.Inclusion criteria were previous complete androgen blockade,anti-androgen (flutamide) withdrawal evaluation,and clinical or biochemical disease progression.The therapy was continued until there was evidence of disease progression or the patients could not tolerate the adverse effects of the medications. Results All the 9 patients had a mean follow-up of 7.5 months.PSA levels decreased by at least 50%,from pre-treatment of (90.5?43.6)ng/ml to post-treatment of (24.8?22.2)ng/ml,in 4 patients. The mean duration of response was 6.8 months (range,2-15 months).An objective response was obtained in 2 patients (1 of CR and 1 of PR).Toxic and adverse effects were minimal. Conclusions The combination of oral VP16 and CPM may be an efficacious and well-tolerated regimen in patients with HRPC.
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50% for more than 1 month as effective,and the efficacy for soft tissue metastases were classified as complete,partial remission,stabilization and progression.Results All patients were followed up for 6-24 months(mean,12 months) with the evaluation of efficacy and toxicity.PSA levels decreased by at least 50% in 6 of 12 cases(50%);it decreased from(63.9?47.3)ng/ml before treatment to(14.4?8.8)ng/ml after treatment,with a mean duration of response being 7.5 months(range,5-12 months).Partial remission of soft tissue metastases was obtained in 2 cases;the metastatic lesions were reduced from 4.0 cm?5.0 cm,(3.0cm?)(3.5) cm to 2.0 cm?2.0 cm,1.0 cm?1.5 cm,respectively,by the treatment,with response duration being 3 and 8 months,respectively.Toxicities were minimal with leukopenia at grade Ⅰ in 1 case,anemia at grade Ⅰ in 1,baldness at grade Ⅰ in 1,nausea at grade Ⅰ in 2 and impaired liver function at grade Ⅱ in 1.Conclusions The combination of oral estramustine phosphate and oral etoposide may be an effective and well-tolerated regimen in patients with HRPC.
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PURPOSE: Corticosteroids suppress the pituitary production of adrenocorticotropic hormone resulting in decreased adrenal steroid production, including adrenal androgens. Ketoconazole is an imidazole fungal agent that inhibit both testicular and adrenal androgenesis. Its primary mechanism of action is inhibition of a cytochrome P450 dependent step in the steroid synthesis pathway, although it has also been reported to have a direct cytotoxic effect in vitro. The effect of further adrenal androgen blockade with ketoconazole plus prednisolone was studied in 9 patients with prostatic cancer who previously progressed after standard hormone therapy. MATERIALS AND METHODS: We treated 9 patients who had hormone refractory metastatic prostate cancer(goserelin acetate, 3 cases; combined goserelin acetate and flutamide, 6 cases) with 200 mg ketoconazole orally every 8 hours and 5 mg prednisolone orally every 12 hours. Mean follow-up period was 6 months(1-15 months). Results: Overall, of 8 evaluable patients 3 had greater than a 50% decrease, 2 had stable and 3 had increase in PSA. The median duration of response was 4 months. Pain was improved in 4 patients. Ketoconazole was generally well tolerated. Toxicity was mild. Nausea with vomiting, edema and hepatotoxicity occurred in 6, 4, 1 patients, respectively. Only 1 patient was withdrawn due to possible ketoconazole-related toxicity. CONCLUSIONS: We concluded that ketoconazole with prednisolone may be a useful treatment modality for management of patients with hormone refractory prostatic cancer.