Apalutamide, enzalutamide, and darolutamide for non-metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis

Abstract Management of non-metastatic castration-resistant prostate cancer (nmCRPC) has undergone a paradigm shift with next-generation androgen receptor inhibitors. However, direct comparative data are not available to inform treatment decisions and/or guideline recommendations. Therefore, we performed network meta-analysis to indirectly compare the efficacy and safety of currently available treatments. Multiple databases were searched for articles published before June 2020. Studies that compared overall and/or metastasis-free and/or prostate-specific antigen (PSA) progression-free survival (OS/MFS/PSA-PFS) and/or adverse events (AEs) in nmCRPC patients were considered eligible. Three studies (n = 4117) met our eligibility criteria. Formal network meta-analyses were conducted. For MFS, apalutamide, darolutamide, and enzalutamide were significantly more effective than placebo, and apalutamide emerged as the best option (P score: 0.8809). Apalutamide [hazard ratio (HR): 0.85, 95% credible interval (CrI): 0.77–0.94] and enzalutamide (HR: 0.86, 95% CrI: 0.78–0.95) were both significantly more effective than darolutamide. For PSA-PFS, all three agents were statistically superior to placebo, and apalutamide emerged as the likely preferred option (P score: 1.000). Apalutamide (HR: 0.71, 95% CrI: 0.69–0.74) and enzalutamide (HR: 0.76, 95% CrI: 0.74–0.79) were both significantly more effective than darolutamide. For AEs (including all AEs, grade 3 or grade 4 AEs, grade 5 AEs, and discontinuation rates), darolutamide was the likely best option. Apalutamide and enzalutamide appear to be more efficacious agents for therapy of nmCRPC, while darolutamide appears to have the most favorable tolerability profile. These findings may facilitate individualized treatment strategies and inform future direct comparative trials.

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Comparing the clinical efficacy and safety of abiraterone and enzalutamide in metastatic castration-resistant prostate cancer: A systematic review and meta-analysis

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155220929414 ◽

2020 ◽

pp. 107815522092941

Author(s):

Xin Wang ◽

Hui Yang ◽

Xiaopeng Hu ◽

Wei Wang ◽

Xiaojia Yu ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Meta Analysis ◽

Specific Antigen ◽

Progression Free Survival ◽

New Drugs ◽

Efficacy And Safety ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Number Of Patients

Background Two new drugs, abiraterone and enzalutamide, had recently shown beneficial effects on survival in patients with metastatic castration-resistant prostate cancer. We systematically reviewed the efficacy and safety of abiraterone and enzalutamide in metastatic castration-resistant prostate cancer in real-world practice. Methods A search from PubMed, Web of Science, Cochrane, Embase was conducted up to 6 March 2019. Available articles from conferences were searched. The endpoint was prostate-specific antigen response, overall survival, progression-free survival, number of patients with any adverse event. Results Fourteen cohort studies involving 3469 participants were included. Pooled result showed that prostate-specific antigen response was higher for patients receiving enzalutamide than abiraterone (790 patients, odds ratio (OR) 0.47, 95% confidence interval (CI) 0.29–0.77, P = 0.003, I2=59%). Enzalutamide was significantly associated with increased adverse events rate in comparison with abiraterone (730 patients, OR 0.35, 95%CI 0.13–0.92, P = 0.03, I2=65%). There was no statistical difference between abiraterone and enzalutamide with respect to perceived cognitive impairments (1856 patients, OR 0.90, 95%CI 0.29–2.76, P = 0.85, I2=5%). Enzalutamide was significantly associated with increased fatigue risk in comparison with abiraterone (2477 patients, OR 0.46, 95%CI 0.34–0.63, P＜0.00001, I2=0%). Conclusions Our results demonstrated that enzalutamide was more efficacious than abiraterone for patients with metastatic castration-resistant prostate cancer, but was associated with a significantly elevated risk of side effects, particularly fatigue.

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Combined CTLA-4 and PD-L1 blockade in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer is associated with increased myeloid and neutrophil immune subsets in the bone microenvironment

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-002919 ◽

2021 ◽

Vol 9 (10) ◽

pp. e002919

Author(s):

Sumit K Subudhi ◽

Bilal A Siddiqui ◽

Ana M Aparicio ◽

Shalini S Yadav ◽

Sreyashi Basu ◽

...

Keyword(s):

Prostate Cancer ◽

Adverse Events ◽

Specific Antigen ◽

Progression Free Survival ◽

Immune Checkpoints ◽

Castration Resistant Prostate Cancer ◽

Bone Microenvironment ◽

Castration Resistant ◽

Number Of Patients ◽

Measurable Disease

BackgroundImmune checkpoint therapy (ICT) has low response rates in patients with metastatic castration-resistant prostate cancer (mCRPC), in part due to few T cells in the tumor microenvironment (TME). Anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) promotes intratumoral T cell infiltration but induces upregulation of PD-1 and programmed death ligand-1 (PD-L1) within the prostate TME. Combined anti-CTLA-4 plus anti-PD-1 can partly overcome this adaptive resistance and was recently shown to augment responses in patients with mCRPC with measurable disease. Although bone is the most common site of metastasis in prostate cancer, patients with bone-predominant disease are frequently excluded from trials because they lack measurable disease, which limits assessment of disease progression and tissue sampling. We therefore designed this study to investigate combined ICT in mCRPC to bone.HypothesisCombined anti-CTLA-4 (tremelimumab) plus anti-PD-L1 (durvalumab) is safe and well tolerated in patients with chemotherapy-naïve mCRPC to bone.Patients and methodsIn this single-arm pilot study, men with chemotherapy-naïve mCRPC to bone received tremelimumab (75 mg intravenous) plus durvalumab (1500 mg intravenous) every 4 weeks (up to four doses), followed by durvalumab (1500 mg intravenous) maintenance every 4 weeks (up to nine doses). The primary endpoint was incidence of adverse events. Secondary endpoints included serum prostate-specific antigen (PSA), progression-free survival (PFS), radiographic PFS (rPFS), and maximal PSA decline.ResultsTwenty-six patients were treated between August 8, 2017 and March 28, 2019. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 11 patients (42%), with no grade 4 or 5 events. TRAEs leading to discontinuation occurred in three patients (12%). PSA decline ≥50% occurred in three patients (12%). Six patients (24%) achieved stable disease for >6 months. At a median follow-up of 43.6 months, median rPFS was 3.7 months (95% CI: 1.9 to 5.7), and median overall survival was 28.1 months (95% CI: 14.5 to 37.3). Post-treatment evaluation of the bone microenvironment revealed transcriptional upregulation in myeloid and neutrophil immune subset signatures and increased expression of inhibitory immune checkpoints.ConclusionsTremelimumab plus durvalumab was safe and well tolerated in patients with chemotherapy-naïve mCRPC to bone, with potential activity in a small number of patients as measured by rPFS. Combination of CTLA-4 and PD-L1 blockade with therapies targeting the myeloid compartment or other inhibitory immune receptors may be necessary to overcome mechanisms of resistance within prostate bone microenvironment.Trial registration numberNCT03204812.

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Cabazitaxel for Metastatic Castration-Resistant Prostate Cancer: Retrospective Data Analysis from an Indian Centre

Case Reports in Oncology ◽

10.1159/000447710 ◽

2016 ◽

Vol 9 (2) ◽

pp. 506-515

Author(s):

Vanita Noronha ◽

Amit Joshi ◽

Vamshi Krishna Muddu ◽

Vijay Maruti Patil ◽

Kumar Prabhash

Keyword(s):

Prostate Cancer ◽

Specific Antigen ◽

Progression Free Survival ◽

Castration Resistant Prostate Cancer ◽

Free Survival ◽

Castration Resistant ◽

Retrospective Data Analysis ◽

Grade 3 ◽

Named Patient Programme

Objective: To determine the efficacy and safety of cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) patients from the named patient programme (NPP) at our centre. Methods: mCRPC patients who progressed on docetaxel were given cabazitaxel intravenously every 3 weeks until disease progression or unacceptable toxicity occurred. Overall survival, progression-free survival, prostate-specific antigen response, quality of life (QOL) changes, and safety were reported. Results: Nine men received cabazitaxel (median: 7 cycles; range: 1–27) under the NPP and were followed until death. Median survival was 14.07 months (1.07–23.80) and progression-free survival was 2.67 months (1.07–20.27). QOL was stable for most patients. Common adverse events (grade ≥3) were neutropenia (n = 8), anaemia (n = 4), and leucopenia (n = 4). Conclusion: These data from 9 patients are consistent with the results reported in the TROPIC study with a manageable safety profile.

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Low-Dose Docetaxel Combined with Dexamethasone Is Feasible for Patients with Castration-Resistant Prostate Cancer

Chemotherapy ◽

10.1159/000440942 ◽

2015 ◽

Vol 61 (1) ◽

pp. 23-31 ◽

Cited By ~ 4

Author(s):

Noriyoshi Miura ◽

Nozomu Tanji ◽

Yutaka Yanagihara ◽

Terutaka Noda ◽

Seiji Asai ◽

...

Keyword(s):

Prostate Cancer ◽

Low Dose ◽

Specific Antigen ◽

Progression Free Survival ◽

Hematological Toxicity ◽

Castration Resistant Prostate Cancer ◽

Gastric Bleeding ◽

Castration Resistant ◽

Analgesic Agents ◽

Grade 3

Aim: Docetaxel-based chemotherapy against castration-resistant prostate cancer (CRPC) has recently been shown to be effective and tolerable. The objective of this study was to retrospectively evaluate the efficacy and toxicity of low-dose docetaxel in combination with dexamethasone. Methods: Thirty-seven CRPC patients were administered a treatment regimen consisting of 50 mg/m2 docetaxel once every 3-4 weeks and 1 mg dexamethasone daily at our institution, between November 2004 and April 2014. Results: Twenty-four patients (65%) had a decrease in serum prostate-specific antigen (PSA) >50%. The median overall survival (OS) and PSA progression-free survival were 26.2 and 10.0 months, respectively. Ten of 12 patients (83%) taking analgesic agents reduced their intake because of decreased pain levels. Grade 3 febrile neutropenia occurred in 2 patients (5%). Nonhematological toxicities were less frequent but sometimes severe. Treatment-related death occurred in 2 octogenarian patients, 1 due to gastric bleeding and the other due to infective endocarditis. Conclusion: Low-dose docetaxel in combination with dexamethasone is feasible in Japanese CRPC patients. Hematological toxicity is less than that seen with standard docetaxel therapy, but it is necessary to monitor patients for severe nonhematological toxicities, particularly very elderly patients.

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Safety and Efficacy of First-Line Treatments for Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Indirect Comparison

BioMed Research International ◽

10.1155/2017/3941217 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Haofeng Zheng ◽

Jialiang Chen ◽

Wenhan Qiu ◽

Sijie Lin ◽

Yanxiong Chen ◽

...

Keyword(s):

Prostate Cancer ◽

Clinical Trials ◽

Specific Antigen ◽

Indirect Comparison ◽

Progression Free Survival ◽

Optimal Order ◽

Castration Resistant Prostate Cancer ◽

First Line ◽

Safety And Efficacy ◽

Castration Resistant

Recently, several drugs have been introduced for the first-line treatment of chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), but few studies have compared treatment outcomes directly. This indirect comparison among 10 clinical trials (n= 4870 patients) retrieved from PubMed, Web of Science, Cochrane Collaboration, and ClinicalTrails.gov was performed to assess the safety and efficacy of docetaxel, cabazitaxel, abiraterone, enzalutamide, and sipuleucel-T for the initial treatment of mCRPC. No significant differences in primary outcome (overall survival) were found among initial treatments. However, docetaxel had the highest probability (37.53%) of being the most effective, but at the cost of more adverse events, while enzalutamide was associated with the best secondary outcomes (prostate-specific antigen response, progression-free survival, quality of life, and adverse event profile). Thus, docetaxel is recommended as the first agent used for the chemotherapy of mCRPC, while enzalutamide is recommended as the first nonchemotherapy treatment. Additional clinical trials are needed to confirm these findings and establish the optimal order for multidrug treatment of mCRPC.

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Efficacy and Safety of Abiraterone Acetate and Enzalutamide for the Treatment of Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.732599 ◽

2021 ◽

Vol 11 ◽

Author(s):

ZhenHeng Wei ◽

ChuXin Chen ◽

BoWen Li ◽

YongYue Li ◽

Hong Gu

Keyword(s):

Prostate Cancer ◽

Systematic Review ◽

Prostate Specific Antigen ◽

Meta Analysis ◽

Specific Antigen ◽

Abiraterone Acetate ◽

Efficacy And Safety ◽

Castration Resistant Prostate Cancer ◽

Randomized Controlled ◽

Castration Resistant

ObjectiveThe androgen receptor-targeting drugs abiraterone acetate and enzalutamide have shown positive results as treatments for metastatic castration-resistant prostate cancer (mCRPC). Therefore, a meta-analysis was conducted to compare the efficacy and safety of abiraterone acetate and enzalutamide in patients with mCRPC.MethodsWe retrieved relevant articles from PubMed, Cochrane, and EMBASE published before December 31, 2020. Eleven articles were initially selected, and four phase III, double-blind, randomized controlled trials of abiraterone acetate and enzalutamide that involved 5199 patients with mCRPC were included. The end points were time to prostate-specific antigen progression (TTPP), according to the prostate-specific antigen working group criteria; overall survival (OS); and radiographic progression-free survival (rPFS).ResultsFour randomized, controlled clinical trials involving 5199 patients were included in this study. The results of the meta-analysis showed that compared with placebo alone, abiraterone significantly improved OS (HR=0.69, 95% CI: 0.60-0.8, P<0.00001), rPFS (HR=0.64, 95% CI: 0.57-0.71, P < 0.00001), and TTPP (HR=0.52, 95% CI: 0.45-0.59, P < 0.00001) in patients with mCRPC. Compared with placebo, enzalutamide significantly improved OS (HR=0.67, 95% CI: 0.59-0.75, P<0.00001), rPFS (HR=0.33, 95% CI: 0.29-0.37, P< 0.00001), and TTPP (HR=0.19, 95% CI: 0.17-0.22, P < 0.00001). An indirect comparison was performed to compare the efficacy of abiraterone and enzalutamide. The results showed that there was no significant difference between abiraterone and enzalutamide with regard to improving the OS of patients with mCRPC (HR=1.03, 95% CI: 0.854-1.242). Enzalutamide was superior to abiraterone with regard to improving rPFS in patients with mCRPC (HR=0.516, 95% CI: 0.438-0.608). With regard to improving TTPP, the efficacy of enzalutamide was better than that of abiraterone (HR=0.365, 95% CI: 0.303-0.441). In sAE, there was no difference between abiraterone and enzalutamide (P=0.21, I2 = 38%).ConclusionsCompared with placebo, both abiraterone and enzalutamide significantly prolonged OS, rPFS, and TTPP in patients with mCRPC. There was no difference in safety between abiraterone and enzalutamide. In addition, enzalutamide had better efficacy than abiraterone with regard to improving rPFS and TTPP but not OS, but the level of evidence was low. Therefore, a large direct comparison trial is needed to compare the efficacy of the two drugs.Systematic Review RegistrationPROSPERO, identifier (CRD42021226808)

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Efficacy and safety of abiraterone acetate plus prednisolone in patients with early metastatic castration-resistant prostate cancer who failed first-line androgen-deprivation therapy: a single-arm, phase 4 study

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyaa225 ◽

2020 ◽

Author(s):

K Kobayashi ◽

N Okuno ◽

G Arai ◽

H Nakatsu ◽

A Maniwa ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Androgen Deprivation Therapy ◽

Specific Antigen ◽

Progression Free Survival ◽

Abiraterone Acetate ◽

Androgen Deprivation ◽

Castration Resistant Prostate Cancer ◽

First Line ◽

Castration Resistant

Abstract Aim The aim was to evaluate the efficacy and safety of abiraterone acetate plus prednisolone in patients with chemotherapy-naïve early metastatic castration-resistant prostate cancer who failed first-line androgen deprivation therapy. Methods Patients with early metastatic castration-resistant prostate cancer with confirmed prostate-specific antigen progression within 1-year or prostate-specific antigen progression without having normal prostate-specific antigen level (<4.0 ng/mL) during first-line androgen deprivation therapy were enrolled and administered abiraterone acetate (1000 mg) plus prednisolone (10 mg). A minimum of 48 patients were required according to Simon’s minimax design. The primary endpoint was prostate-specific antigen response rate (≥50% prostate-specific antigen decline by 12 weeks), secondary endpoints included prostate-specific antigen progression-free survival and overall survival. Safety parameters were also assessed. Results For efficacy, 49/50 patients were evaluable. Median age was 73 (range: 55–86) years. The median duration of initial androgen deprivation therapy was 32.4 (range: 13.4–84.1) weeks and 48 patients experienced prostate-specific antigen progression within 1-year after initiation of androgen deprivation therapy. prostate-specific antigen response rate was 55.1% (95% confidence interval: 40.2%–69.3%), median prostate-specific antigen–progression-free survival was 24.1 weeks, and median overall survival was 102.9 weeks (95% confidence interval: 64.86 not estimable [NE]). Most common adverse event was nasopharyngitis (15/50 patients, 30.0%). The most common ≥grade 3 adverse event was alanine aminotransferase increased (6/50 patients, 12.0%). Conclusions Abiraterone acetate plus prednisolone demonstrated a high prostate-specific antigen response rate of 55.1%, suggesting tumor growth still depends on androgen synthesis in patients with early metastatic castration-resistant prostate cancer. However, prostate-specific antigen–progression-free survival was shorter than that reported in previous studies. Considering the benefit–risk profile, abiraterone acetate plus prednisolone would be a beneficial treatment option for patients with chemotherapy-naive metastatic prostate cancer who show early castration resistance.

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The hematologic parameters in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.308 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 308-308

Author(s):

Onal Cem ◽

Ali Murat Sedef ◽

Fatih KOse ◽

Ezgi Oymak ◽

Ozan Cem Guler ◽

...

Keyword(s):

Prostate Cancer ◽

Univariate Analysis ◽

Specific Antigen ◽

Progression Free Survival ◽

Abiraterone Acetate ◽

Castration Resistant Prostate Cancer ◽

Characteristic Analysis ◽

Lymphocyte Ratio ◽

Castration Resistant ◽

Psa Response

308 Background: The aim of this study is to evaluate the prognostic implications of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at baseline and after 4 and 12 weeks of treatment with abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: We retrospectively evaluated 102 mCRPC treated with abiraterone either pre- or post-chemotherapy between November 2012 and October 2017 in three institutions. We calculated NLR and PLR at baseline and at 4 and 12 weeks after initiation of abiraterone, and we evaluated prostate-specific antigen (PSA) response every 4 weeks. Fifty patients (49%) were treated with abiraterone post-docetaxel, and 52 patients (51%) received abiraterone pre-chemotherapy. Based on receiver operating characteristic analysis, patients were stratified as low NLR ( < 3.1) or high NLR (≥ 3.1), and low PLR ( < 163) or high PLR (≥ 163). The cutoff for anemia was < 12g/dL. Results: Median follow-up times for patients overall and for those who survived were 24.0 months (range, 0.3 – 54.9 months) and 25.5 months (range, 2.8 – 54.9 months), respectively. The median time of abiraterone treatment was 8.1 months (range, 2.4 – 40.1 months). The median overall survival (OS) was 20.8 months (interquartile range: 17.3–24.4). In univariate analysis, NLR, PLR, PSA response, and low hemoglobin (Hgb) were found significantly predictive of OS and progression-free survival (PFS). In multivariate analysis, declines in NLR and PSA of ≥ 90% emerged as significant independent predictors of OS and PFS. High-NLR patients who remained high or who returned to low NLR after 4 and 12 weeks showed significantly worse OS than patients with low baseline NLR. Patients with baseline Hgb > 12 g/dL had significantly longer median OS compared with patients with Hgb ≤ 12 g/dL; however, the significance of Hgb was lost at 12 weeks. Conclusions: NLR and PSA response to abiraterone was a significant predictor of OS and PFS in mCRPC patients treated with abiraterone delivered either pre- or post-chemotherapy. Furthermore, persistent increase in NLR during abiraterone has prognostic value for OS in patients with mCRPC.

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Sequential Therapy with Docetaxel and Cabazitaxel Starting at Low PSA Levels was Associated with Longer Survival in Patients with Castration-Resistant Prostate Cancer

10.21203/rs.3.rs-562897/v1 ◽

2021 ◽

Author(s):

Naoki Terada ◽

Atsuro Sawada ◽

Hiroaki Kawanisi ◽

Takeru Fujimoto ◽

Toshihiro Magaribuchi ◽

...

Keyword(s):

Prostate Cancer ◽

Survival Rates ◽

Specific Antigen ◽

Progression Free Survival ◽

Sequential Therapy ◽

Optimal Timing ◽

Castration Resistant Prostate Cancer ◽

Time To Progression ◽

Decrease Rate ◽

Castration Resistant

Abstract Background: This study investigated the optimal timing for starting docetaxel (DOC) and cabazitaxel (CBZ) by examining the correlation of their efficacy and evaluating factors associated with the prognosis of patients with castration-resistant prostate cancer (CRPC) receiving DOC-CBZ sequential treatment.Methods: We retrospectively evaluated data for 146 patients who received DOC followed by CBZ. The correlations of prostate specific antigen (PSA) decrease rate and time to progression between DOC and CBZ treatment were examined. The association of parameters with progression-free survival (PFS) and overall survival (OS) were evaluated. Survival rates were compared between patients with high and low PSA levels at the start of DOC and CBZ treatment.Results: No correlations of PSA decrease rate and time to progression were observed between DOC and CBZ. In multivariate analyses, higher PSA level at the start of DOC was significantly associated with shorter PFS (P = 0.004) and OS (P = 0.001). The OS of patients who started DOC and CBZ at low PSA levels was significantly longer than those that started at high PSA levels (P = 0.002 and P = 0.003). In patients who started DOC at high PSA levels, those who switched to CBZ at low PSA levels had longer OS than those who switched at high PSA levels (P = 0.048).Conclusions: For patients for whom DOC was not effective, sequential CBZ might reduce PSA for a long duration. Starting DOC and switching to CBZ at low PSA levels might result in improved prognoses in CRPC patients.Trial registration: This study was registered retrospectively.

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Efficacy of Combination Chemotherapy With Docetaxel, Estramustine and Carboplatin in Men With Castration-resistant Prostate Cancer

Cancer Diagnosis & Prognosis ◽

10.21873/cdp.10060 ◽

2021 ◽

Vol 1 (5) ◽

pp. 451-457

Author(s):

KATSUYA HIKITA ◽

MASASHI HONDA ◽

RYUTARO SHIMIZU ◽

SHOGO TERAOKA ◽

BUNYA KAWAMOTO ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Cancer Progression ◽

Specific Antigen ◽

Treatment Protocol ◽

Area Under The Curve ◽

Progression Free Survival ◽

Castration Resistant Prostate Cancer ◽

Free Survival ◽

Castration Resistant

Background: The efficacy of docetaxel and carboplatin with oral estramustine was evaluated in patients with castration-resistant prostate cancer. Patients and Methods: Patients were treated with intravenous docetaxel at 30 mg/m2 on days 1, 8, 15, and 22 of a 28-day cycle. Intravenous carboplatin (area under the curve, 6 mg/ml/min) was administered on day 1. Patients received oral estramustine at 626.8 mg/day throughout the treatment protocol. Patients were evaluated for response, with treatment continued until cancer progression or onset of severe adverse events. Results: Twenty patients with castration-resistant prostate cancer were treated for a median of 3.5 cycles. Prostate-specific antigen decreased by more than 30% in 18 patients, including 14 patients with a decrease of more than 50%. Median overall survival was 11 months, prostate-specific antigen progression-free survival was 6.5 months, and radiographic progression-free survival was 7 months. Conclusion: Docetaxel and carboplatin with oral estramustine shows efficacy against castration-resistant prostate cancer.

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