Phase-II Study of Docetaxel, Estramustine Phosphate, and Carboplatin in Patients with Hormone-Refractory Prostate Cancer

Kikuno, Nobuyuki; Urakami, Shinji; Nakamura, Shigeru; Hiraoka, Takeo; Hyuga, Taijyu; Arichi, Naoko; Wake, Koji; Sumura, Masahiro; Yoneda, Tatsuaki; Kishi, Hirofumi; Shigeno, Kazushi; Shiina, Hìroaki; Igawa, Mikio

doi:10.1016/j.eururo.2006.12.030

Cited by 27 publications

(24 citation statements)

References 25 publications

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“…We believe that treatment with DGP is better than single agent docetaxel for patients with CRMPC, and hypothesise that, in a clinical setting in which DGP treatment is introduced immediately after the diagnosis of metastatic, CRPC disease, even if the patient being asymptomatic, the DGP treatment probably would improve overall survival and PSA response. Nobuyuki et al reported that levels of PSA decreased by more than 50% in 95% of patients with hormone refractory prostate cancer and a median overall survival of 26.6 months, when treated with docetaxel, estramustine phosphate and carpoplatin [22]. This study and similar phase II studies of combination chemotherapy for CRMPC patients have proven effective and with acceptable toxicity [23,24] and thus warrants further studies.…”

Section: Discussionsupporting

confidence: 55%

Phase I/II study on docetaxel, gemcitabine and prednisone in castrate refractory metastatic prostate cancer

Buch-Hansen

Bentzen

Hansen

et al. 2009

Cancer Chemother Pharmacol

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Purpose:We assessed the efficacy and toxicity of a fixed dose of docetaxel and prednisone, combined with escalating doses of gemcitabine (DGP). The primary endpoint was PSA response. Methods:Fifteen patients (pts) were enrolled in the phase I and 50 pts entered the phase II. Pts were given DGP, maximum of 8 courses, until progression or unacceptable toxicity. Docetaxel 75 mg/m 2 was administered intravenously day 1, gemcitabine was given day 1 and 8 in doses increasing from 600 to 1,000 mg/m 2 every third week. Pts had castrate refractory metastatic prostate cancer (CRMPC), adequate function of liver, kidney and bone marrow; ECOG performance status ≤2 and were chemotherapy-naïve. Results:Median age was 64 range (49-77). Twenty-one (42%) were PS 0, 26 (52%) were PS 1 and 3 (6%) were PS 2. The median pre-treatment PSA was 448 (12-4.580). No dose limiting toxicity was observed even with the highest dose level in the phase I part of the study. In the phase II part, PSA response was observed in 37(74%) pts. Twenty-four (48%) pts had measurable disease; 12 (50%) had partial remission, 5 (21%) had stable disease, 7 (29%) were not evaluable. Time to progression (TTP) was 7.9 months and overall survival (OS) was 13.9 months. Thirty-seven pts (74%) developed neutropenia, non-haematological toxicity was modest. Conclusions:The PSA response rate was promising and the toxicity of DGP was manageable; however OS was comparable to results of treatment with single agent docetaxel.

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Section: Discussionsupporting

confidence: 55%

Phase I/II study on docetaxel, gemcitabine and prednisone in castrate refractory metastatic prostate cancer

Buch-Hansen

Bentzen

Hansen

et al. 2009

Cancer Chemother Pharmacol

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“…When used alone to treat HRPC, it has shown response rates ranging from 19% to 69% (1). EM has also shown promising activity against HRPC in combination with other drugs and is currently undergoing clinical trials in combination with docetaxel, etoposide, carboplatin, and vinblastine (2,3). Fizazi and colleagues (2007) have reported that the overall survival rate for metastatic HRPC is significantly increased when EM is combined with docetaxel, paclitaxel, vinblastine, or ixabepilone rather than used by itself (4).…”

Section: Introductionmentioning

confidence: 99%

Kinetic Stabilization of Microtubule Dynamics by Estramustine Is Associated with Tubulin Acetylation, Spindle Abnormalities, and Mitotic Arrest

2008

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Estramustine (EM) alone or in combination with other anticancer agents is clinically used for the treatment of hormone refractory prostate cancer. Furthermore, EM has been shown to potently inhibit the proliferation of different types of cancer cells in culture apparently by targeting microtubules; however, the antiproliferative mechanism of action of EM is not clear. In this work, we have shown that EM strongly suppressed the dynamic instability of individual microtubules in MCF-7 cells by reducing the rates of growing and shortening excursions and increasing the time microtubule spent in the pause state. At its half maximal proliferation inhibitory concentration (IC 50 ), EM exerted strong suppressive effects on the dynamics of microtubules in MCF-7 cells without detectably affecting either the organization or the polymerized mass of microtubules. At relatively high concentrations (5 Â IC 50 ), EM significantly depolymerized microtubules in the cells. Furthermore, the microtubules were found highly acetylated, supporting the conclusion that they were stabilized by the drug. EM treatment induced spindle abnormalities in MCF-7 cells, and a major population of the arrested mitotic cells was multipolar. EM also perturbed the microtubule-kinetochore interaction, thereby activating the spindle assembly checkpoint and leading to apoptotic cell death. [Cancer Res 2008; 68(15):6181-9]

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“…With the exception of the Oh et al [15] Cancer and Leukemia Group B (CALGB) trial, patients may have received prior chemotherapy, and 16% of patients across all trials were reported to have received prior chemotherapy. In the Kelly et al [12] and Solit et al [14] trials, estramustine-and taxanebased regimens were allowed, and in the Urakami et al [13] and Kikuno et al [18] trials, most chemotherapy-treated patients received estramustinebased regimens. The majority of patients were enrolled from June 1997 to December 2001, with only the Oh et al [16] Individual patient-level data were requested for the seven trials.…”

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confidence: 99%

Efficacy of carboplatin–taxane combinations in the management of castration-resistant prostate cancer: a pooled analysis of seven prospective clinical trials

et al. 2010

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Background: Docetaxel is associated with prolonged survival in castration-resistant prostate cancer (CRPC).Platinum compounds have modest but distinct single-agent activity. Carboplatin may have greatest potential for benefit when combined with taxanes. We investigated whether there is a subset of patients with CRPC for whom the efficacy of combination taxane-estramustine-carboplatin (TEC) chemotherapy may be greatest.Patients and methods: Individual patient data (n = 310) were obtained from seven trials using TEC chemotherapy.Prostate-specific antigen (PSA) response was defined as ‡50% post-therapy decline from baseline. Overall survival was defined from baseline to death from any cause. Logistic and Cox regression were used to investigate heterogeneity in outcome to TEC by patient and disease characteristics. Predicted survival probabilities were calculated from the Halabi Cancer and Leukemia Group B (CALGB) nomogram. Results:The pooled PSA response proportion was 69% [95% confidence interval (CI) 56% to 80%]. There was no evidence of differential PSA response by disease characteristics. Established prognostic factors were associated with survival. The pooled 12-month survival estimate of 79% (95% CI 71% to 84%) was higher than the median 59% 12-month nomogram-predicted survival.Conclusions: TEC chemotherapy has significant clinical activity in CRPC. A randomized, controlled trial evaluating the addition of carboplatin to taxane-based chemotherapy is needed to elucidate the value of carboplatin in CRPC.

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Phase-II Study of Docetaxel, Estramustine Phosphate, and Carboplatin in Patients with Hormone-Refractory Prostate Cancer

Cited by 27 publications

References 25 publications

Phase I/II study on docetaxel, gemcitabine and prednisone in castrate refractory metastatic prostate cancer

Phase I/II study on docetaxel, gemcitabine and prednisone in castrate refractory metastatic prostate cancer

Kinetic Stabilization of Microtubule Dynamics by Estramustine Is Associated with Tubulin Acetylation, Spindle Abnormalities, and Mitotic Arrest

Efficacy of carboplatin–taxane combinations in the management of castration-resistant prostate cancer: a pooled analysis of seven prospective clinical trials

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