Docetaxel In Metastatic Castration-resistant Prostate Cancer Research Articles

Docetaxel Treatment in PTEN- and ERG-aberrant Metastatic Prostate Cancers

BackgroundLoss of PTEN is a common genomic aberration in castration-resistant prostate cancer (CRPC) and is frequently concurrent with ERG rearrangements, causing resistance to next-generation hormonal treatment (NGHT) including abiraterone. The relationship between PTEN loss and docetaxel sensitivity remains uncertain. ObjectiveTo study the antitumor activity of docetaxel in metastatic CRPC in relation to PTEN and ERG aberrations. Design, setting, and participantsSingle-centre, retrospective analysis of PTEN loss and ERG expression using a previously described immunohistochemistry (IHC) binary classification system. Patients received docetaxel between January 1, 2006 and July 31, 2016. Outcome measurements and statistical analysisResponse correlations were analyzed using Pearson's χ2 tests and independent-sample t tests. Overall (OS) and progression-free survival (PFS) were analyzed using univariate and multivariate (MVA) Cox regression and Kaplan-Meier methods. Results and limitationsOverall, 215 patients were eligible. Established metastatic CRPC prognostic factors were well balanced between PTEN loss (39%) and normal patients (61%). PTEN loss was associated with shorter median OS (25.4 vs 34.7 mo; hazard ratio [HR] 1.66, 95% confidence interval [CI] 1.18–2.13; p=0.001). There were no differences in median PFS (8.0 vs 9.1 mo; univariate HR 1.20, 95% CI 0.86–1.68; p=0.28) and PSA response (53.4% vs 50.6%; p=0.74). PTEN loss was an independent prognostics factor in MVA. ERG status was available for 100 patients. ERG positivity was not associated with OS or PFS. Limitations include the retrospective nature and the single-centre analysis. ConclusionsOur findings suggest that metastatic CRPC with PTEN loss might benefit more from docetaxel than from NGHT. Patient summaryIn this study we found that metastatic prostate cancer with loss of the PTEN switch may benefit more from docetaxel than from abiraterone.

Prolonged treatment with three-weekly docetaxel plus daily prednisolone for metastatic castration-resistant prostate cancer: a multicenter, phase II, open-label, non-comparative, extension study in Japan

There are few reports of long-term treatment with docetaxel in castration-resistant prostate cancer (CRPC) because of the limit of a maximum of ten cycles of treatment in TAX327 showing a survival benefit. Therefore, this study, ARD6563, was conducted to evaluate the safety of more than ten cycles of docetaxel in metastatic CRPC. We enrolled patients who had received ten cycles of docetaxel in the preceding study, ARD6562. For ARD6563, patients received docetaxel every 3weeks, at the last dose (70, 60, or 50mg/m(2)) received for cycle 10 in ARD6562, with prednisolone 5mg orally twice daily. The safety analysis set comprised 15 patients (median age, 64years; performance status, 0 in 87%) out of 43 patients treated in ARD6562. The median initial dose of docetaxel was 60mg/m(2), and the median number of additional cycles administered was 8 (range, 1-42). The relative dose intensity was 78.0% for docetaxel and 98.0% for prednisolone. Dose reduction was needed in 3 cycles because of grade 3 infection, febrile neutropenia, and grade 2 neuropathy. Administration delay was necessitated in 6 cycles because of grade 1-2 nonhematological toxicities. The major grade 3-4 toxicities were myelosuppression. Five patients who had an observed partial response or stable disease in ARD6562 maintained their clinical response in ARD6563. The study treatment was discontinued in 10 patients because of disease progression and in 4 patients for serious toxicities. There were no treatment-related deaths. Long-term docetaxel with prednisolone is feasible in selected Japanese patients with CRPC.

Gemcitabine and docetaxel in metastatic, castrate‐resistant prostate cancer

Docetaxel is the standard of care for patients with metastatic, castrate-resistant prostate cancer (CRPC). Gemcitabine is a nucleoside analogue with broad antitumor activity. In a phase 2 study of combined docetaxel and gemcitabine, the authors assessed its safety and activity in patients with chemotherapy-naive, metastatic CRPC. Eligible patients had untreated, metastatic CRPC with radiologic and/or biochemical evidence of progression after antiandrogen withdrawal with castrate testosterone levels, an Eastern Cooperative Oncology performance status (ECOG PS) of 0 to 2, and adequate organ function; no previous chemotherapy was permitted. Patients received gemcitabine (800 mg/m²) Days 1 and 8 and docetaxel (75 mg/m²) on Day 8 every 21 days for a maximum of 6 cycles. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) for measurable disease. A prostate-specific antigen (PSA) response was defined as a decline ≥ 50% in baseline PSA level. Thirty-five patients with chemotherapy-naive, metastatic CRPC were enrolled. The median age was 67 years, and 60% of patients had an ECOG PS of 0. PSA responses were observed in 49% of patients. Among the patients who had measurable disease (n = 25), 3 patients (12%) had a confirmed, RECIST-defined partial response (PR); 4 patients (16%) had an unconfirmed PR; and 15 patients (60%) achieved stable disease. The most common adverse events included grade 1 and 2 fatigue (69%), alopecia (80%), and nausea/vomiting (54%). No treatment-related deaths were noted, but an unusually high incidence of grade 3 and 4 neutropenia was observed. The efficacy of combined gemcitabine and docetaxel in metastatic CRPC was similar to that observed with single-agent docetaxel. In contrast to single-agent docetaxel, the combination was moderately toxic and had an impact primarily on bone marrow reserve.

Carboplatin plus paclitaxel therapy after docetaxel in men with metastatic castrate resistant prostate cancer

Objectives Docetaxel is considered first-line chemotherapy for patients with metastatic castrate resistant prostate cancer (CRPC). Carboplatin and paclitaxel have demonstrated activity in CRPC but published data are limited regarding use after docetaxel. Methods A retrospective, bi-institutional review was conducted of patients with advanced CRPC treated with carboplatin plus paclitaxel after docetaxel. Therapy was evaluated for tolerability, response, and survival. Endpoints used modified Prostate Cancer Working Group 2 criteria. Results Twenty-five patients were identified from February 2000 to March 2008. Median pretreatment PSA was 130.2 ng/ml [range 0.1–2100]. Sites of metastases included bone (88%), lymph nodes (52%), pelvis (32%), lung (28%), and liver (20%). A median 4.5 cycles of docetaxel [range 1–22] were given with a median progression-free survival (PFS) of 12 weeks [range 2–68]. Eighty-eight percent of patients (22/25) were docetaxel-refractory at the initiation of therapy with carboplatin (AUC 4–6) day 1 plus paclitaxel 60–80 mg/m 2 days 1, 8, and 21 recycled every 28 days. Patients received a median of 3.5 cycles [range 1–8] of carboplatin/paclitaxel with a median PFS of 12 weeks [range 2–35]. Sixty-four percent of patients (16/25) achieved ≥30% reduction in PSA with a median overall survival of 42 weeks [95% CI 30.6–53.5 weeks]. Grade 3 or 4 adverse hematologic events occurred in 11/25 (44%) patients, with no neutropenic fever or grade 3/4 non-hematologic toxicity. Conclusion Carboplatin/paclitaxel chemotherapy following docetaxel in metastatic CRPC is well tolerated with favorable PSA response rates and survival. This combination is a viable option after progression on docetaxel-based therapy.

Docetaxel in the management of prostate cancer: current standard of care and future directions

Background: Advanced and metastatic prostate cancer continues to represent a significant healthcare burden. Since the publication of two randomized trials that showed significant survival and palliative benefits for men treated with docetaxel, this drug has become the treatment of choice for patients with metastatic castration resistant prostate cancer (CRPC). Objective: This review discusses the development and current use of docetaxel in metastatic CRPC, as well as future clinical applications. Methods: The current literature, meeting abstracts and ClinicalTrials.gov have been reviewed. The most relevant studies involving patients with prostate cancer receiving therapy with docetaxel, alone or in combination with other agents, have been summarised. Conclusion: Docetaxel monotherapy is the approved treatment for patients with metastatic CRPC, and its association with other agents, such as targeted therapies, is currently under study. Several trials are currently ongoing to investigate the use of docetaxel in the early stages of disease, particularly in the neoadjuvant and adjuvant settings for patients with high-risk disease.