Addition of docetaxel or bisphosphonates to standard of care in men with localised or metastatic, hormone-sensitive prostate cancer: a systematic review and meta-analyses of aggregate data.
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SUBMITTER: Vale CL
PROVIDER: S-EPMC4737894 | biostudies-literature | 2016 Feb
REPOSITORIES: biostudies-literature
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Addition of docetaxel or bisphosphonates to standard of care in men with localised or metastatic, hormone-sensitive prostate cancer: a systematic review and meta-analyses of aggregate data.
Vale Claire L CL Burdett Sarah S Rydzewska Larysa H M LHM Albiges Laurence L Clarke Noel W NW Fisher David D Fizazi Karim K Gravis Gwenaelle G James Nicholas D ND Mason Malcolm D MD Parmar Mahesh K B MKB Sweeney Christopher J CJ Sydes Matthew R MR Tombal Bertrand B Tierney Jayne F JF
The Lancet. Oncology 20151221 2
<h4>Background</h4>Results from large randomised controlled trials combining docetaxel or bisphosphonates with standard of care in hormone-sensitive prostate cancer have emerged. In order to investigate the effects of these therapies and to respond to emerging evidence, we aimed to systematically review all relevant trials using a framework for adaptive meta-analysis.<h4>Methods</h4>For this systematic review and meta-analysis, we searched MEDLINE, Embase, LILACS, and the Cochrane Central Regist ...[more]
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Project description:BackgroundMost men who die of prostate cancer are older than 70 years. The ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) randomized men of all ages with metastatic hormone-sensitive prostate cancer (mHSPC) to receive androgen deprivation therapy (ADT) with or without docetaxel demonstrating an overall survival (OS) benefit for docetaxel.MethodsIn a post-hoc analysis of this trial, we assessed patient characteristics and OS in patients ≥70 years ("older men") versus <70 years ("younger men") with Cox proportional hazards models. In addition, we compared adverse events, therapy completion rate, and subsequent treatment patterns between these two groups using Chi-squared tests.Results177 (22.4%) patients were ≥70 years. Docetaxel + ADT resulted in improved OS in both older and younger men (Hazard Ratio [HR] 0.45, 95%CI: 0.25-0.80 for older men; HR 0.71, 95%CI: 0.53-0.95 for younger men). This treatment benefit was seen for subgroups of older men with high volume disease (HR 0.43, 95%CI 0.23-0.79) and de novo metastatic disease (HR 0.36, 95%CI 0.19-0.69). A similar proportion of older and younger men completed six cycles of docetaxel (82.6% vs. 87.1%, p = 0.28). Rates of grade 3-5 adverse events were similar between older and younger men (36.8% vs. 26.8%, respectively, p = 0.069). The rate of any Grades 4-5 adverse events did not differ significantly between older and younger men (14.9% vs. 11.9%, respectively, p = 0.46). In the control arm, a smaller proportion of older men received subsequent cancer treatments (34.4% vs. 51.5%, p = 0.017) or subsequent docetaxel (25.6% vs. 37.6%, p = 0.035) compared to younger men.ConclusionsOlder men with mHSPC had similar OS benefit and clinical outcomes compared to younger men when receiving docetaxel + ADT. Oncologists should consider docetaxel chemotherapy as a favorable treatment option for older men with mHSPC who are fit for chemotherapy.
| S-EPMC8599519 | biostudies-literature
Project description:BackgroundCurrently, metastatic hormone-sensitive prostate cancer (mHSPC) patients are often treated with docetaxel chemotherapy at the initiation of hormonal therapy. This treatment is based on the results of two pivotal trials. However, trial populations are not a representative of real-world patient populations.ObjectiveWe aimed to analyze whether survival rates in our daily practice cohort is comparable with those in clinical trials and to characterize the tolerability of docetaxel chemotherapy in daily practice.Design setting and participantsIn this retrospective cohort analysis, we studied 159 mHSPC patients treated with early docetaxel from April 2014 up to June 2020 in a top clinical hospital in The Netherlands. Patients were selected using hospital pharmacy records.Outcome measurements and statistical analysisWe compared the results of our cohort with the results of the cohorts of the two pivotal trials. We aimed to analyze the survival rates in our cohort and characterize the tolerability of docetaxel chemotherapy in daily practice.Results and limitationsDespite the relatively high number of comorbidities in our daily practice cohort, overall survival of our cohort showed great similarity with that of the two pivotal trials: 60.2 mo compared with 57.6 and 59.1 mo. Furthermore, early docetaxel was well tolerated in daily practice. Nearly 90% of the patients completed the full six cycles, and polyneuropathy led to relatively few dose reductions (6.9%).ConclusionsEarly docetaxel is well tolerated in daily practice. Our daily practice cohort showed great similarity in overall survival to the clinical trials. Our results might be of interest in the developing landscape of mHSPC treatment.Patient summaryWe studied docetaxel chemotherapy for metastatic prostate cancer in daily practice. These patients have the same survival as selected patients participating in clinical trials. Docetaxel was well tolerated in daily practice.
| S-EPMC8546919 | biostudies-literature
Project description:BackgroundAddition of docetaxel to androgen deprivation therapy (ADT) for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has been proved to be effective with an overall survival (OS) benefit in phase III clinical trials. The effectiveness of docetaxel with ADT in the general patient population remains unknown.ObjectiveThe purpose of this study is to report the clinical experience in mHSPC patients treated with 3rd-weekly docetaxel plus ADT in routine practice at two Danish institutions.Design setting and participantsA two-center retrospective study including consecutive mHSPC patients treated with 3rd-weekly docetaxel plus ADT was conducted.Outcome measurements and statistical analysisOutcomes of interest were OS, and biochemical and clinical progression-free survival.Results and limitationsA total of 173 consecutive patients with mHSPC who received docetaxel every 3rd week plus ADT between June 2015 and February 2018 were included. Most patients had high-volume disease (85%). All six planned docetaxel cycles were delivered in 149 cases (86%). Of the patients, 106 (61%) were alive at the last follow-up. At a median follow-up of 42 (37.8-58.6) mo, the median OS was 51.6 (41.5-56.3) mo. Castration-resistant prostate cancer (CRPC) developed in 46% within 1 yr, with a median time to CRPC of 15.6 (13.0-18.1) mo. Prostate-specific antigen nadir ≤0.2 ng/l was achieved in 15% of patients after 6 mo of ADT and in 19% after 12 mo.ConclusionsThe effect of docetaxel for mHSPC patients treated in routine practice appears comparable with the overall efficacy reported in the literature. Selection of patients will influence the results in clinical practice and clinical studies.Patient summaryIn this report, we looked at the clinical effectiveness of docetaxel combined with androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer (mHSPC) in a Danish population. We found the effect of docetaxel treatment for mHSPC in the general population to be comparable with the overall efficacy reported in published studies.
| S-EPMC8317901 | biostudies-literature
Project description:BackgroundAndrogen-deprivation therapy (ADT) historically represented the milestone for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). Recently, combining androgen receptor-targeted agents (ARTA) or docetaxel with ADT significantly improved clinical outcomes in this setting. The efficacy of the combined use of an ARTA with docetaxel and ADT (triplet), however, was unknown, and often conflicting data derived from subgroup analysis of randomized phase III trials. In order to better define the benefits and risks of the triplet in mHSPC, we carried out a systematic review and meta-analysis of available clinical trials.MethodsA literature search with no data restriction using Medline/PubMed, the Cochrane Library, and American Society of Clinical Oncology/European Society for Medical Oncology (ASCO/ESMO) Meeting abstracts was carried out up to April 2022. The meta-analysis was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statements. Overall survival (OS) was the primary endpoint; progression-free survival (PFS) and safety were secondary endpoints. For OS and PFS, summary hazard ratios (HRs) were calculated; for safety, risk ratio (RR) was assessed. Random- or fixed-effects models were used, depending on studies heterogeneity.ResultsFive randomized clinical trials fulfilled the prespecified inclusion criteria. The triplet significantly improved OS (fixed-effect, HR = 0.74; P < 0.00001) and PFS (fixed-effect; HR = 0.50 for clinical PFS, HR = 0.49 for radiological PFS; P < 0.0001) compared with docetaxel plus ADT. We did not show heterogeneity between treatment efficacy and the disease burden, metachronous versus synchronous presentation, concomitant versus sequential strategy. Compared with docetaxel + ADT, the triplet did not increase the risk of adverse events (AEs) (RR = 1.00, P = 0.27 for any-grade AEs; RR = 1.13, P = 0.14 for severe AEs), except for severe hypertension (RR = 1.73, P = 0.001).ConclusionsEmerging evidence supports the combination of an ARTA plus docetaxel and ADT in mHSPC patients. Given the availability of several strategies in this setting, clinical characteristics and drug safety profile may help clinicians select the appropriate treatment for mHSPC patients who are more likely to benefit from treatment intensification.
| S-EPMC9588886 | biostudies-literature
Project description:BackgroundSTAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients.MethodsWe randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC + docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional.ResultsBetween 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n = 724) or SOC + docetaxel (n = 362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2 months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR = 0.81, 95% CI 0.69-0.95, P = 0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P = 0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR = 0.66, 95% CI 0.57-0.76, P < 0.001) and progression-free survival (HR = 0.69, 95% CI 0.59-0.81, P < 0.001) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P > 0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression).ConclusionsThe clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden.
| S-EPMC6938598 | biostudies-literature
Project description:PurposeRecently, docetaxel treatment of metastatic prostate cancer patients shifted towards the hormone-sensitive stage of the disease. There are contradictive reports on differences in toxicity of docetaxel in metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC) patients. Possible differences in toxicity might be attributed to different pharmacokinetics (PK) in the two patient populations.MethodsPatients with mCRPC or mHSPC and a standard indication for docetaxel treatment were included in the study. All patients had suppressed serum testosterone levels (≤ 0.5 ng/mL or 1.73 nmol/L). Venous blood samples were obtained at the first docetaxel treatment, until 48 h after infusion. Plasma concentrations of docetaxel, unbound docetaxel and docetaxel metabolites were measured using validated liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) assays and compared between the two groups. Moreover, serum levels of docetaxel transporting α1-acid glycoprotein were measured and docetaxel toxicity recorded.ResultsA total of ten mCRPC and nine mHSPC patients were included in the study. The two cohorts differed in the number of prior treatments and opiate use, which were higher for mCRPC patients. The docetaxel PK was not different between mCRPC and mHSPC patients, with areas under the plasma concentration versus time curve (AUC0-48) 1710 [coefficient of variation (CV) 28.4%] and 1486 (CV 25.2%) ng/mL*h (p = 0.27), respectively. Also, the PK profile of unbound docetaxel, M1/M3, M2 and M4 metabolites were similar in both groups. Docetaxel doses were reduced in 50% of the mCRPC patients and 11% of the mHSPC patients.ConclusionThe PK profile of docetaxel was similar in mCPRC and mHSPC patients. Therefore, possible differences in toxicity between mCRPC and mHSPC patients cannot be explained by differences in docetaxel PK in our study population. These results suggest that treatment adaptations are not recommended in the new population of patients with mHSPC.
| S-EPMC9135852 | biostudies-literature
Project description:The increasing knowledge of prostate cancer is leading to many questions about its natural history and to reconsider conventional therapeutic strategies. Androgen ablation therapy has been the standard therapy in the advanced setting. Although docetaxel has demonstrated increased survival in patients with metastatic prostate cancer who had progressed to hormone treatments, due to its potential toxicity the role of chemotherapy has been relegated to patients who were symptomatic or who had high tumor burden. Several studies have assessed whether docetaxel could have a role in hormone-sensitive disease or even in earlier stages with no distant metastases. In the CHAARTED and STAMPEDE studies, docetaxel provides an unprecedented increase in overall survival (OS). This review summarizes the evidence behind the paradigm shift to strengthening docetaxel as a new standard of treatment that prolongs survival in earlier stages of prostate cancer.
| S-EPMC5424862 | biostudies-literature
Project description:BackgroundDocetaxel (D) or secondary hormonal therapy (SHT) each combined with androgen deprivation therapy (ADT) represent possible treatment options in males with metastasized hormone-sensitive prostate cancer (mHSPC). Real-world data comparing different protocols are lacking yet. Thus, our objective was to compare the efficacy and safety of abiraterone acetate (AA)+ADT versus D+ADT in mHSPC.MethodsIn a retrospective multicenter analysis including males with mHSPC treated with either of the aforementioned protocols, overall survival (OS), progression-free survival 1 (PFS1), and progression-free survival 2 (PFS2) were assessed for both cohorts. Median time to event was tested by Kaplan-Meier method and log-rank test. The Cox-proportional hazards model was used for univariate and multivariate regression analyses.ResultsOverall, 196 patients were included. The AA+ADT cohort had a longer PFS1 in the log-rank testing (23 vs. 13 mos., p < 0.001), a longer PFS2 (48 vs. 33 mos., p = 0.006), and longer OS (80 vs. 61 mos., p = 0.040). In the multivariate analyses AA+ADT outperformed D+ADT in terms of PFS1 (HR = 0.34, 95% CI = 0.183-0.623; p = 0.001) and PFS2 (HR = 0.33 95% CI = 0.128-0.827; p = 0.018), respectively, while OS and toxicity rate were similar between both groups.ConclusionsAA+ADT is mainly associated with a similar efficacy and overall toxicity rate as D+ADT. Further prospective research is required for validation of the clinical value of the observed benefit of AA+ADT for progression-free end-points.
| S-EPMC8446402 | biostudies-literature
Project description:IntroductionDocetaxel is the first-line drug that has been proved to improve the overall survival of men with metastatic hormone-sensitive prostate cancer (mHSPC). For patients who survive the prostate cancer, they may be at risk of secondary neoplasm, especially for the therapy-related myelodysplastic syndrome or therapy-related acute myeloid leukemia (t-AML).Case presentationWe reported a 44-year-old man with prostate cancer (cT4N1M1c) who developed t-AML following docetaxel chemotherapy. Typically, the t-AML in our case was characterized by an aberrant karyotype t(15;17)(q22;q21).ConclusionsThis case is, to our knowledge, the first time to report a patient with mHSPC who developed therapy-related acute promyelocytic leukemia following docetaxel chemotherapy, suggesting that docetaxel might contribute to the induction of t-AML.
| S-EPMC11731904 | biostudies-literature
Project description:BACKGROUNDMetastatic hormone-sensitive prostate cancer (mHSPC) is androgen dependent, and its treatment includes androgen deprivation therapy (ADT) with gonadal testosterone suppression. Since 2014, overall survival (OS) has been prolonged with addition of other systemic therapies, such as adrenal androgen synthesis blockers, potent androgen receptor blockers, or docetaxel, to ADT. HSD3B1 encodes the rate-limiting enzyme for nongonadal androgen synthesis, 3β-hydroxysteroid dehydrogenase-1, and has a common adrenal-permissive missense-encoding variant that confers increased synthesis of potent androgens from nongonadal precursor steroids and poorer prostate cancer outcomes.METHODSOur prespecified hypothesis was that poor outcome associated with inheritance of the adrenal-permissive HSD3B1 allele with ADT alone is reversed in patients with low-volume (LV) mHSPC with up-front ADT plus addition of androgen receptor (AR) antagonists to inhibit the effect of adrenal androgens. HSD3B1 genotype was obtained in 287 patients with LV disease treated with ADT + AR antagonist only in the phase III Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer (ENZAMET) trial and was associated with clinical outcomes.RESULTSPatients who inherited the adrenal-permissive HSD3B1 allele had more favorable 5-year clinical progression-free survival and OS when treated with ADT plus enzalutamide or ADT plus nonsteroidal antiandrogen compared with their counterparts who did not have adrenal-permissive HSD3B1 inheritance. HSD3B1 was also associated with OS after accounting for known clinical variables. Patients with both genotypes benefited from early enzalutamide.CONCLUSIONThese data demonstrated an inherited physiologic driver of prostate cancer mortality is associated with clinical outcomes and is potentially pharmacologically reversible.FUNDINGNational Cancer Institute, NIH; Department of Defense; Prostate Cancer Foundation, Australian National Health and Medical Research Council.
| S-EPMC11405037 | biostudies-literature