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European Urology Oncology Apr 2024It remains unclear to what extent the therapy of the primary local tumor, such as radical prostatectomy (RP) and radiation therapy (RT), improves overall survival in... (Review)
Review
CONTEXT
It remains unclear to what extent the therapy of the primary local tumor, such as radical prostatectomy (RP) and radiation therapy (RT), improves overall survival in patients with low-volume metastatic hormone-sensitive prostate cancer (mHSPC). However, data suggest a benefit of these therapies in preventing local events secondary to local tumor progression.
OBJECTIVE
To evaluate the efficacy of adding local therapy (RP or RT) to systemic therapies, including androgen deprivation therapy, docetaxel, and/or androgen receptor axis-targeted agents, in preventing local events in mHSPC patients compared with systemic therapy alone (ie, without RT of the prostate or RP).
EVIDENCE ACQUISITION
Three databases and meeting abstracts were queried in November 2023 for studies analyzing mHSPC patients treated with local therapy. The primary outcome of interest was the prevention of overall local events (urinary tract infection, urinary tract obstruction, and gross hematuria) due to local disease progression. Subgroup analyses were conducted to assess the differential outcomes according to the type of local therapy (RP or RT).
EVIDENCE SYNTHESIS
Overall, six studies, comprising two randomized controlled trials, were included for a systematic review and meta-analysis. The overall incidence of local events was significantly lower in the local treatment plus systemic therapy group than in the systemic therapy only groups (relative risk [RR]: 0.50, 95% confidence interval [CI]: 0.28-0.88, p = 0.016). RP significantly reduced the incidence of overall local events (RR: 0.24, 95% CI: 0.11-0.52) and that of local events requiring surgical intervention (RR: 0.08, 95% CI: 0.03-0.25). Although there was no statistically significant difference between the RT plus systemic therapy and systemic therapy only groups in terms of overall local events, the incidence of local events requiring surgical intervention was significantly lower in the RT plus systemic therapy group (RR: 0.70, 95% CI: 0.49-0.99); local events requiring surgical intervention of the upper urinary tract was significantly lower in local treatment groups (RR: 0.60, 95% CI: 0.37-0.98, p = 0.04). However, a subgroup analysis revealed that neither RP nor RT significantly impacted the prevention of local events requiring surgical intervention of the upper urinary tract.
CONCLUSIONS
In some patients with mHSPC, RP or RT of primary tumor seems to reduce the incidence of local progression and events requiring surgical intervention. Identifying which patients are most likely to benefit from local therapy, and at what time point (eg, after response of metastases), will be necessary to set up a study assessing the risk, benefits, and alternatives to therapy of the primary tumor in the mHSPC setting.
PATIENT SUMMARY
Our study suggests that local therapy of the prostate, such as radical prostatectomy or radiotherapy, in patients with metastatic hormone-sensitive prostate cancer can prevent local events, such as urinary obstruction and gross hematuria.
PubMed: 38575408
DOI: 10.1016/j.euo.2024.03.007 -
Frontiers in Pharmacology 2021To evaluate the efficacy and safety of anti-PD-1/PD-L1 Inhibitors versus docetaxel for non-small cell lung cancer by meta-analysis. Randomized controlled trials (RCTs)...
To evaluate the efficacy and safety of anti-PD-1/PD-L1 Inhibitors versus docetaxel for non-small cell lung cancer by meta-analysis. Randomized controlled trials (RCTs) about anti-PD-1/PD-L1 Inhibitors versus docetaxel on the treatment of NSCLC were searched in CNKI, WF, VIP, PubMed, EMBASE, Cochrane Library, and Web of Science databases. Two reviewers independently screened literature, extracted data and evaluated the risk of bias of eligible studies. Meta-analysis was performed by RevMan5.3 software. Compared with the use of docetaxel chemotherapy for NSCLC, the overall survival and progression-free survival of the anti-PD-1/PD-L1 Inhibitors regimen are better [overall survival: (HR= 0.73, 95%CI:0.69∼0.77, P<0.00001], progression-free survival: (HR= 0.89, 95%CI:0.83∼0.94, P<0.00001]), and lower incidence of treatment-related grade 3 or higher adverse events ([OR=0.20, 95% CI: 0.13∼0.31, P<0.00001]). Compared with the docetaxel chemotherapy regimen, the anti-PD-1/PD-L1 Inhibitors has certain advantages in terms of efficacy and safety. The results still need to be confirmed by a multi-center, large sample, and high-quality research.
PubMed: 34456725
DOI: 10.3389/fphar.2021.699892 -
Frontiers in Pharmacology 2023In the last few decades, there has been a rapid development in cancer therapies and improved detection strategies, hence the death rates caused by cancer have...
In the last few decades, there has been a rapid development in cancer therapies and improved detection strategies, hence the death rates caused by cancer have decreased. However, it has been reported that cardiovascular disease has become the second leading cause of long-term morbidity and fatality among cancer survivors. Cardiotoxicity from anticancer drugs affects the heart's function and structure and can occur during any stage of the cancer treatments, which leads to the development of cardiovascular disease. To investigate the association between anticancer drugs for non-small cell lung cancer (NSCLC) and cardiotoxicity as to whether: different classes of anticancer drugs demonstrate different cardiotoxicity potentials; different dosages of the same drug in initial treatment affect the degree of cardiotoxicity; and accumulated dosage and/or duration of treatments affect the degree of cardiotoxicity. This systematic review included studies involving patients over 18 years old with NSCLC and excluded studies in which patients' treatments involve radiotherapy only. Electronic databases and registers including Cochrane Library, National Cancer Institute (NCI) Database, PubMed, Scopus, Web of Science, ClinicalTrials.gov and the European Union Clinical Trials Register were systematically searched from the earliest available date up until November 2020. A full version protocol of this systematic review (CRD42020191760) had been published on PROSPERO. A total of 1785 records were identified using specific search terms through the databases and registers; 74 eligible studies were included for data extraction. Based on data extracted from the included studies, anticancer drugs for NSCLC that are associated with cardiovascular events include bevacizumab, carboplatin, cisplatin, crizotinib, docetaxel, erlotinib, gemcitabine and paclitaxel. Hypertension was the most reported cardiotoxicity as 30 studies documented this cardiovascular adverse event. Other reported treatment-related cardiotoxicities include arrhythmias, atrial fibrillation, bradycardia, cardiac arrest, cardiac failure, coronary artery disease, heart failure, ischemia, left ventricular dysfunction, myocardial infarction, palpitations, and tachycardia. The findings of this systematic review have provided a better understanding of the possible association between cardiotoxicities and anticancer drugs for NSCLC. Whilst variation is observed across different drug classes, the lack of information available on cardiac monitoring can result in underestimation of this association. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020191760, identifier PROSPERO CRD42020191760.
PubMed: 37383708
DOI: 10.3389/fphar.2023.1137983 -
European Urology Focus Mar 2022Novel prospective randomized controlled observations addressing combination therapy in metastatic hormone-sensitive prostate cancer (mHSPC) have demonstrated promising... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Novel prospective randomized controlled observations addressing combination therapy in metastatic hormone-sensitive prostate cancer (mHSPC) have demonstrated promising overall survival (OS) outcomes.
OBJECTIVE
To compare these novel findings and systematically review and address them within formal network meta-analyses (NMAs) that include observations from other prospective randomized controlled trials (RCTs).
EVIDENCE ACQUISITION
First, we focused on abiraterone, enzalutamide, apalutamide, and docetaxel effects on OS in mHSPC using the PRISMA methodology. PubMed and abstracts identified prospective RCTs in first-line mHSPC. Second, we focused on mature studies that reached median OS and tested OS between abiraterone and docetaxel with tumor burden stratification.
EVIDENCE SYNTHESIS
The first part included seven studies (n = 6639) and the second part, five studies (n = 4462). In the first part, abiraterone ranked first for high-volume mHSPC. Conversely, enzalutamide ranked first for low-volume mHSPC. In the second part, abiraterone treatment in high-volume mHSPC resulted in median OS of 50.1 mo and exceeded that with docetaxel (45.9 mo) and ADT alone (34.0 mo). Docetaxel treatment in low volume mHSPC resulted in median OS of 69.5 mo versus 67.7 mo with ADT alone.
CONCLUSIONS
In conventional NMA that relied on conventional hazard ratios, differences were identified with respect to the relative efficacy of the combination therapies examined; abiraterone dominated the alternatives in high-volume mHSPC. In part two, which relied on trials for which median OS is available, comparison of abiraterone versus docetaxel revealed a 4-mo difference in OS in high-volume mHSPC. Conventional NMA may have overestimated the importance of treatment efficacy instead of focusing on median OS duration, which might represent a more important clinical endpoint.
PATIENT SUMMARY
We reviewed studies on hormonal treatments and chemotherapy used for prostate cancer that has spread outside the prostate gland (metastatic prostate cancer, mPC). We found that the best overall survival was with the hormone agents abiraterone in high-volume mPC and enzalutamide in low-volume mPC. In comparison to the chemotherapy drug docetaxel, median overall survival with abiraterone was 4 months longer among patients with mPC.
Topics: Androgen Antagonists; Docetaxel; Hormones; Humans; Male; Network Meta-Analysis; Prostatic Neoplasms
PubMed: 33853754
DOI: 10.1016/j.euf.2021.04.003 -
Metabolism: Clinical and Experimental Sep 2022Several anticancer agents have been associated with cardiac toxic effects. The currently proposed mechanisms to explain cardiotoxicity differ among anticancer agents,... (Review)
Review
Several anticancer agents have been associated with cardiac toxic effects. The currently proposed mechanisms to explain cardiotoxicity differ among anticancer agents, but in fact, the specific modulation is not completely elucidated. Thus, this systematic review aims to provide an integrative perspective of the molecular mechanisms underlying the toxicity of anticancer agents on heart muscle while using a high-throughput technology, mass spectrometry (MS)-based proteomics. A literature search using PubMed database led to the selection of 27 studies, of which 13 reported results exclusively on animal models, 13 on cardiomyocyte-derived cell lines and only one included both animal and a cardiomyocyte line. The reported anticancer agents were the proteasome inhibitor carfilzomib, the anthracyclines daunorubicin, doxorubicin, epirubicin and idarubicin, the antimicrotubule agent docetaxel, the alkylating agent melphalan, the anthracenedione mitoxantrone, the tyrosine kinase inhibitors (TKIs) erlotinib, lapatinib, sorafenib and sunitinib, and the monoclonal antibody trastuzumab. Regarding the MS-based proteomic approaches, electrophoretic separation using two-dimensional (2D) gels coupled with tandem MS (MS/MS) and liquid chromatography-MS/MS (LC-MS/MS) were the most common. Overall, the studies highlighted 1826 differentially expressed proteins across 116 biological processes. Most of them were grouped in larger processes and critically analyzed in the present review. The selection of studies using proteomics on heart muscle allowed to obtain information about the anticancer therapy-induced modulation of numerous proteins in this tissue and to establish connections that have been disregarded in other studies. This systematic review provides interesting points for a comprehensive understanding of the cellular cardiotoxicity mechanisms of different anticancer drugs.
Topics: Animals; Antineoplastic Agents; Cardiotoxicity; Chromatography, Liquid; Proteomics; Tandem Mass Spectrometry
PubMed: 35809654
DOI: 10.1016/j.metabol.2022.155250 -
Frontiers in Oncology 2022Adding induction chemotherapy to concurrent platinum-based chemoradiotherapy has significantly prolonged the survival time of patients with locoregionally advanced...
BACKGROUND
Adding induction chemotherapy to concurrent platinum-based chemoradiotherapy has significantly prolonged the survival time of patients with locoregionally advanced nasopharyngeal carcinoma. In this study, we intend to evaluate the survival outcomes, responses, and incidences of toxicities of induction chemotherapy and the differences between different strategies.
METHODS
A comprehensive search was conducted in PubMed, Embase, Web of Science, and Cochrane CENTRAL on August 10, 2021. Single-arm or multi-arm prospective clinical trials on induction chemotherapy without targeted therapies or immune checkpoint inhibitors were included. Primary outcomes included survival outcomes, objective response rate, and disease control rate, and the secondary outcome was the rates of grade 3 or higher treatment-related adverse events.
RESULTS
The 39 studies included in the systematic review and meta-analysis comprised 36 clinical trials and 5389 patients. The estimates for 3-year overall and fail-free survival rates were 87% and 77%. The estimates for 5-year rates of overall and fail-free survival were 81% and 73%. Gemcitabine plus platinum and docetaxel combined with 5-fluorouracil plus platinum strategies were associated with the highest rates of 3-year and 5-year overall survival. The objective response and disease control rates were 85% and 98% after the completion of induction chemotherapy. Neutropenia (27%) and nausea/vomiting (7%) were the most common grade 3 or higher treatment-related hematological and non-hematological adverse events during the induction phase.
CONCLUSIONS
Different induction chemotherapeutic strategies appear to have varying effects and risks; a comprehensive summary of the survival outcomes, responses, and toxicities in clinical trials may provide a crucial guide for clinicians.
PubMed: 35965543
DOI: 10.3389/fonc.2022.927510 -
Frontiers in Oncology 2023In the REVEL trial, ramucirumab plus docetaxel demonstrated significant improvements in overall survival (OS), progression-free survival (PFS), and overall response rate...
INTRODUCTION
In the REVEL trial, ramucirumab plus docetaxel demonstrated significant improvements in overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) compared with placebo plus docetaxel for treatment of metastatic non-small cell lung cancer (NSCLC) that progressed during or after platinum-based chemotherapy. Since the approval of ramucirumab plus docetaxel, immune checkpoint inhibitors (ICIs), either as single agents or in combination with chemotherapy, have become the standard of care for first-line treatment of patients with advanced NSCLC. However, efficacy and safety data for ramucirumab plus docetaxel after prior ICI treatment from randomized controlled clinical studies are lacking.
METHODS
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic literature review was performed. Electronic databases and select international oncology conference proceedings were searched. Studies published between 01 January 2014 and 01 July 2022, which evaluated 2 efficacy outcomes (and included at least 1 time-to-event endpoint) or safety outcomes of ramucirumab plus docetaxel in NSCLC that progressed after prior ICI treatment, were identified. Twelve studies were included in the analysis. Two treatment groups were selected: ramucirumab plus docetaxel after prior ICI ± chemotherapy (RAM + DTX ICI pre-treated) and ramucirumab plus docetaxel after prior chemotherapy only (RAM + DTX ICI naïve). OS, PFS, ORR, disease control rate (DCR), and safety data were extracted and descriptively summarized across both treatment groups.
RESULTS
The pooled weighted median PFS and median OS were 5.7 months (95% confidence interval [CI]: 3.9-6.8) and 11.2 months (95% CI: 7.5-17.5), respectively, in the RAM + DTX ICI pre-treated group and 3.8 months (95% CI: 2.3-4.1) and 13.5 months (95% CI: 8-24.0), respectively, in the RAM + DTX ICI naïve group. The ORR and DCR ranged from 20.9% to 60.0% and from 62.4% to 90.0%, respectively, in the RAM + DTX ICI pre-treated group and from 17.7% to 20.0% and from 57.1% to 75.0%, respectively, in the RAM + DTX ICI naïve group. The safety profile across studies was consistent between both treatment groups, and no new safety signals were reported.
CONCLUSIONS
Cumulatively, these results support the combination of ramucirumab plus docetaxel as an effective and safe subsequent therapy for the treatment of patients with metastatic NSCLC with disease progression irrespective of previous ICI treatment.
PubMed: 37731641
DOI: 10.3389/fonc.2023.1247879 -
Prostate Cancer and Prostatic Diseases Jun 2024While the addition of androgen receptor signaling inhibitors (ARSIs) to androgen deprivation therapy (ADT) results in better of overall survival in patients with... (Review)
Review
Health-related quality of life in patients with metastatic hormone-sensitive prostate cancer treated with androgen receptor signaling inhibitors: the role of combination treatment therapy.
BACKGROUND
While the addition of androgen receptor signaling inhibitors (ARSIs) to androgen deprivation therapy (ADT) results in better of overall survival in patients with metastatic hormone-sensitive prostate cancer (mHSPC), information regarding health related quality of life (HR-QoL) is sparse. We aimed at summarizing current evidence on the impact of ARSIs on HR-QoL.
METHODS
We performed a systematic review of the published literature on PubMed/EMBASE, Web of Science, SCOPUS, and the Cochrane libraries between January 2011 and April 2022. We included only phase III randomized controlled trials (RCT), which were selected according to the PRISMA guidelines. We aimed at evaluating differences in HR-QoL, assessed by validated patient reported outcomes instruments. We analyzed global scores and sub-domains such as sexual functioning, urinary symptoms, bowel symptoms, pain/fatigue, emotional and social/family wellbeing. We reported data descriptively.
RESULTS
Six RCTs were included: two used enzalutamide with ADT as intervention arms (ARCHES, ENZAMET); one used apalutamide with ADT (TITAN); two abiraterone acetate and prednisone (AAP) with ADT (STAMPEDE, LATITUDE); and one darolutamide with ADT (ARASENS). Enzalutamide or AAP with ADT increase overall HR-QoL in comparison with ADT alone, ADT with first generation nonsteroideal anti-androgens or ADT with docetaxel, whereas apalutamide and darolutamide with ADT maintain HR-QoL similarly to ADT alone or ADT with docetaxel, respectively. Time to first deterioration of pain was longer with combination therapy with enzalutamide, AAP or darolutamide, but not with apalutamide. No worsening of emotional wellbeing was reported from the addition of ARSIs to ADT than ADT alone.
CONCLUSIONS
The addition of ARSIs to ADT in mHSPC tends to increase overall HR-QoL and prolong time to first deterioration of pain/fatigue compared with ADT alone, ADT with first generation nonsteroideal anti-androgens, and ADT with docetaxel. ARSIs show a complex interaction with remaining HR-QoL domains. We advocate a standardization of HR-QoL measurement and reporting to allow further comparisons.
Topics: Humans; Male; Quality of Life; Androgen Receptor Antagonists; Antineoplastic Combined Chemotherapy Protocols; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Androgen Antagonists; Nitriles; Phenylthiohydantoin; Benzamides; Clinical Trials, Phase III as Topic
PubMed: 37055663
DOI: 10.1038/s41391-023-00668-0 -
Gastric Cancer : Official Journal of... Sep 2022Currently, the standard treatment for gastric and gastroesophageal junction (GEJ) adenocarcinoma, including distal esophagus, consists of perioperative chemotherapy (CT)... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Currently, the standard treatment for gastric and gastroesophageal junction (GEJ) adenocarcinoma, including distal esophagus, consists of perioperative chemotherapy (CT) according to FLOT schedule (5FU/leucovorin/oxaliplatin and docetaxel), or of concomitant chemoradiotherapy (CTRT) based on CROSS regimen. However, due to the relatively lack of direct comparisons between perioperative CT and neoadjuvant CTRT, the effectiveness of these new combinations is unknown. Therefore, we performed a network meta-analysis (NMA) to compare the efficacy of different neoadjuvant treatments for gastric and GEJ adenocarcinoma in terms of overall and disease-free survival (OS and DFS).
MATERIALS AND METHODS
We searched MEDLINE, Embase, and Cochrane from database inception until February 1st 2022 for randomized clinical trials that enrolled adults with gastric and GEJ carcinomas and provided data about OS and/or DFS. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (95% CrIs). Surface under the cumulative rank (SUCRA) curve plots were produced. The primary outcome was OS, secondary endpoint DFS.
RESULTS
A total of 1247 citations were screened; 14 randomized clinical trials were included. In Bayesian comparisons, FLOT-based CT ranked as one of the better regimens with a probability of 41%, both with induction CT followed by CTRT (P = 0.45). For DFS analysis, the FLOT regimen was the preferred option (P = 0.62).
CONCLUSIONS
In conclusion, this NMA adds further evidence to the optimization of treatment strategies for gastric and GEJ adenocarcinomas and confirms that incorporation of perioperative triplet-based CT improved both OS and DFS compared to surgery alone and other preoperative strategies.
Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Esophageal Neoplasms; Esophagogastric Junction; Humans; Neoadjuvant Therapy; Network Meta-Analysis; Stomach Neoplasms
PubMed: 35704113
DOI: 10.1007/s10120-022-01314-9 -
Clinical Genitourinary Cancer Dec 2022The management of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has been significantly modified by the availability of innovative but expensive... (Review)
Review
The management of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has been significantly modified by the availability of innovative but expensive treatments, increasing the economic burden of prostate cancer. Here, we aimed to systematically identify and review published economic evaluations (EEs) related to the treatment of mHSPC and assess their quality. A systematic search was performed of the PubMed and Cochrane databases. Three reviewers independently selected EEs by defined inclusion and exclusion criteria. They extracted all data from each EE (general information, study population, data about the EE, interventions and comparators, and outcomes). They also assessed the quality of the selected EEs according to Drummond's checklist. Fourteen EEs published between 2016 and 2021 were eligible for the systematic review. The EEs found ADT + docetaxel to be the most cost-effective of all available treatments as a first-line strategy for mHSPC (abiraterone acetate plus prednisone, enzalutamide, and apalutamide). Five EEs showed that a simple price reduction of abiraterone acetate of 50% to 75% could change the results to render this treatment also cost-effective relative to that with docetaxel. Twelve EEs were of high quality, with a Drummond score ≥ 7. Analysis of the 14 EEs identified by our systematic review, amongst which 78.6% met high quality standards, showed that ADT + docetaxel tends to be the most cost-effective alternative for mHSPC. These results were assessed by sensitivity analysis. The data provided by this systematic review help to provide a better understanding of these treatments and the better use of healthcare resources.
Topics: Male; Humans; Docetaxel; Abiraterone Acetate; Cost-Benefit Analysis; Treatment Outcome; Prostatic Neoplasms; Hormones
PubMed: 35610112
DOI: 10.1016/j.clgc.2022.04.014