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Journal of Gastrointestinal Oncology Apr 2023Chemotherapy plays an important role in definitive chemoradiotherapy strategies. However, the most optimal concurrent chemotherapy scheme is still controversial. This...
Paclitaxel combined with platinum (PTX) versus fluorouracil combined with cisplatin (PF) in the treatment of unresectable esophageal cancer: a systematic review and meta-analysis of the efficacy and toxicity of two different regimens.
BACKGROUND
Chemotherapy plays an important role in definitive chemoradiotherapy strategies. However, the most optimal concurrent chemotherapy scheme is still controversial. This study aimed to systematically evaluate the efficacy and toxicity of paclitaxel/docetaxel combined with platinum (PTX) and fluorouracil combined with cisplatin (PF) in the concurrent chemoradiotherapy (CCRT) of unresectable esophageal cancer.
METHODS
The PubMed, China National Knowledge Infrastructure (CNKI), Google Scholar and Embase databases were searched by combining subject words and free words through December 31, 2021. The inclusion criteria were pathologically confirmed esophageal cancer studies using CCRT, where the chemotherapy regimen only compared PTX and PF. Quality evaluation and data extraction of studies that met the inclusion criteria were carried out independently. Stata 11.1 software was used to perform the meta-analysis. The begger analysis and egger analysis were used to assess publication bias, and the robustness of the pooled results further assessed by the Trim and Fill analysis.
RESULTS
After screening, 13 randomized controlled trials (RCTs) were included. A total of 962 cases were enrolled, including 480 (49.9%) in the PTX group and 482 (50.1%) in the PF group. The gastrointestinal reaction to the PF regimen was the most serious [relative risk (RR) =0.54, 95% confidence interval (CI): 0.36-0.80, P=0.003]. The complete remission (CR) rate, objective response rate (ORR), and disease control rate (DCR) of the PTX group were higher than those of the PF group (RR =1.35, 95% CI: 1.03-1.76, P=0.030; RR =1.12, 95% CI: 1.03-1.22, P=0.006; RR =1.05, 95% CI: 1.01-1.09, P=0.022). In terms of the overall survival (OS) rate, the 2-year survival rates of the PTX group were higher than those of the PF group (P=0.005). There was no significant difference in the 1-, 3-, and 5-year survival rates between the two regimens (P=0.064, 0.144, and 0.341, respectively). There may be publication bias for ORR and DCR, and the results are reversed after applying the Trim and Fill method, so the combined results are not robust.
CONCLUSIONS
PTX may be the preferred regimen for CCRT of esophageal squamous cell carcinoma, with better short-term therapeutic effect and 2-year OS rate and lower gastrointestinal toxicity.
PubMed: 37201087
DOI: 10.21037/jgo-23-33 -
Frontiers in Pharmacology 2023To conduct a systematic review and network meta-analysis (NMA) to compare the efficacy of currently available combination therapies in patients with metastatic...
To conduct a systematic review and network meta-analysis (NMA) to compare the efficacy of currently available combination therapies in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Qualified publications were searched in the PubMed, Embase, and Cochrane CENTRAL databases. Overall survival (OS) and radiographic progression-free survival (rPFS) were indirectly compared and assessed using NMA and the surface under the cumulative ranking curve, respectively. Adverse events (AEs) were also compared. Eighteen publications from 12 trials were analyzed in the NMA. In the overall population, triplet therapy was ranked first for OS (hazard ratio [HR]: 0.57, 95% credible interval [CrI]: 0.48-0.67) and rPFS (HR: 0.33, 95% CrI:0.26-0.41) compared with androgen deprivation therapy (ADT) with or without standard non-steroidal antiandrogen. In high-volume mHSPC, triplet therapy was also ranked first in OS (HR, 0.57; 95% CrI:0.44-0.75) and rPFS(HR, 0.29; 95% CrI: 0.23-0.37). Specifically, abiraterone triplet therapy was ranked first in OS (HR, 0.52; 95% CrI:0.38-0.72) and rPFS (HR, 0.28; 95% CrI:0.21-0.38) among all therapies. ADT plus rezvilutamide was ranked first among doublet therapies (OS: HR, 0.58; 95% CrI:0.44-0.77; rPFS: HR, 0.44; 95% CrI:0.33-0.58). In low-volume mHSPC, doublet and triplet therapies were ranked first in OS (HR:0.68, 95% CrI:0.58-0.80) and rPFS (HR:0.37, 95% CrI:0.25-0.55), respectively. ADT plus apalutamide was ranked first in OS among all therapies (HR:0.53, 95% CrI:0.35-0.79), whereas enzalutamide triplet therapy was ranked first in rPFS (HR:0.27, 95% CrI:0.15-0.51). ADT plus rezvilutamide showed a relatively lower incidence of AE among all therapies (OR:1.00, 95% CrI:0.31-3.15), and a lower risk of specific AEs among doublet therapies, particularly regarding seizure (OR, 0.29; 95% CrI:0.01-8.18) and fatigue (OR, 0.96; 95% CrI:0.63-1.46). Docetaxel-based doublet or triplet therapies significantly increased the risk of any AEs or grade ≥3 AEs. Triplet therapy was the best treatment option for the overall population. In high-volume mHSPC, triplet therapy and ADT plus rezvilutamide had the greatest potential to benefit patients. Patients with low-volume mHSPC were most likely to benefit from ADT plus androgen receptor-targeted agents. Triplet therapy was associated with a higher risk of AEs than the other therapies. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375347, identifier PROSPERO:CRD42022375347.
PubMed: 37153773
DOI: 10.3389/fphar.2023.1148021 -
Cancer Medicine Jul 2023Uterine leiomyosarcoma (uLMS) is an aggressive mesenchymal neoplasm associated with a poor prognosis. Systemic chemotherapy is the standard therapy for patients with... (Meta-Analysis)
Meta-Analysis Review
Uterine leiomyosarcoma (uLMS) is an aggressive mesenchymal neoplasm associated with a poor prognosis. Systemic chemotherapy is the standard therapy for patients with uLMS. However, it is unclear which treatment regimen results in the most favorable clinical outcome. We performed a meta-analysis and meta-regression analysis to assess the efficiency of different treatments received by patients with advanced, metastatic, and relapsing uLMS by evaluating the objective response rate (ORR) and disease control rate (DCR) as primary endpoints. The frequentist random effects meta-analysis model was used to compare the outcomes of different treatment regimens for advanced uLMS. A meta-regression analysis was performed to estimate the association between the study-specific hazard ratios and specific demographic variables. A meta-analysis of 51 reports including 1664 patients was conducted. Among patients who received adjuvant chemotherapy (916 patients; 55%), gemcitabine and docetaxel were the most frequently used drugs. First-line monotherapy with alkylating agents (pooled ORR = 0.48; 95% confidence interval [CI]: 0.44-0.52) and second-line monotherapy with protein kinase inhibitors (pooled ORR = 0.45; 95% CI: 0.39-0.52) resulted in favorable prognoses. The combinations of anthracycline plus alkylating therapy (pooled DCR = 0.74; 95% CI: 0.67-0.79) and of gemcitabine plus docetaxel (pooled DCR = 0.70; 95% CI: 0.63-0.75) showed the greatest benefits when used as first-line and second-line chemotherapies, respectively. Subgroup meta-analysis results revealed that dual-regimen therapies comprising anthracycline plus alkylating therapy and gemcitabine plus docetaxel are practical therapeutic choices for International Federation of Gynecology and Obstetrics stages III-IVb with distant metastases when assessed by computed tomography (p = 0.001). Furthermore, neoadjuvant chemotherapy and local radiotherapy resulted in favorable outcomes for patients with earlier stages of distant relapsed uLMS (p < 0.001). Our findings provide a basis for designing new therapeutic strategies and can potentially guide clinical practice toward better prognoses for uLMS patients with advanced, metastatic, and relapsing disease.
Topics: Female; Humans; Leiomyosarcoma; Docetaxel; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Recurrence, Local; Gemcitabine; Uterine Neoplasms; Proportional Hazards Models; Anthracyclines
PubMed: 37081717
DOI: 10.1002/cam4.5930 -
Annals of Surgical Oncology Jul 2023Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is... (Meta-Analysis)
Meta-Analysis Review
FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review.
BACKGROUND
Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC.
METHODS
We performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based.
RESULTS
A total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC.
CONCLUSIONS
In patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.
Topics: Humans; Gemcitabine; Antineoplastic Combined Chemotherapy Protocols; Oxaliplatin; Pancreatic Neoplasms; Fluorouracil; Leucovorin; Neoadjuvant Therapy; Paclitaxel; Multicenter Studies as Topic
PubMed: 37020094
DOI: 10.1245/s10434-023-13353-2 -
Frontiers in Oncology 2023The best choice of first-line treatment for metastatic hormone-sensitive prostate cancer (mHSPC) is unclear. We aimed to compare the effectiveness and safety determined...
BACKGROUND
The best choice of first-line treatment for metastatic hormone-sensitive prostate cancer (mHSPC) is unclear. We aimed to compare the effectiveness and safety determined in randomized clinical trials of doublet and triplet treatments for mHSPC.
METHODS
Medline, Embase, Cochrane Central and ClinicalTrials.gov were searched from inception through July 01, 2022. Eligible studies were phase III randomized clinical trials evaluating androgen deprivation treatment (ADT) alone, doublet therapies [ADT combined with docetaxel (DOC), novel hormonal agents (NHAs), or radiotherapy (RT)], or triplet therapies (NHA+DOC+ADT) as first-line treatments for mHSPC. Outcomes of interest included overall survival (OS), progression-free survival (PFS) and grades 3-5 adverse events (AEs). Subgroup analyses were performed based on tumor burden. The effects of competing treatments were assessed by Bayesian network meta-analysis using R software.
RESULTS
Ten trials with 12,298 patients comparing nine treatments were included. Darolutamide (DARO) +DOC+ADT ranked best in terms of OS benefits (OR 0·52 [95% CI 0·39-0·70]), but its advantages were all statistically insignificant compared with other therapy options except for DOC+ADT (OR 0·68 [95% CI 0·53-0·88]) and RT+ADT (OR 0·57 [95% CI 0·40-0·80]). In terms of PFS, enzalutamide(ENZA)+DOC+ADT (OR 0·32 [95% CI 0·24-0·44]) and abiraterone and prednisone (AAP) +DOC+ADT (OR 0·33 [95% CI 0·25-0·45]) ranked best. For patients with high volume disease (HVD), low volume disease (LVD), and visceral metastases, the optimal therapies were AAP+DOC+ADT (OR 0·52 [95% CI 0·33-0·83]), apalutamide+ADT (OR 0·52 [95% CI 0·26-1·05]) and DARO+DOC+ADT (OR 0·42 [95% CI 0·13-1·34]), respectively. For safety, AAP+DOC+ADT (OR 3·56 [95% CI 1·51-8·43]) ranked worst with the highest risk of grade 3-5 AEs.
CONCLUSIONS
Triple therapies may further improve OS and PFS but may be associated with a decrease in safety. Triplet therapies could be suggested for HVD patients, while doublet combinations should still be preferred for LVD patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPEROFILES/303117_STRATEGY_20220202.pdf, identifier CRD4202303117.
PubMed: 36959793
DOI: 10.3389/fonc.2023.1104242 -
JAMA Oncology May 2023The effectiveness of triplet therapy compared with androgen pathway inhibitor (API) doublets in a heterogeneous patient population with metastatic castration-sensitive... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The effectiveness of triplet therapy compared with androgen pathway inhibitor (API) doublets in a heterogeneous patient population with metastatic castration-sensitive prostate cancer (mCSPC) is unknown.
OBJECTIVE
To assess the comparative effectiveness of contemporary systemic treatment options for patients with mCSPC across clinically relevant subgroups.
DATA SOURCES
For this systematic review and meta-analysis, Ovid MEDLINE and Embase were searched from each database's inception (MEDLINE, 1946; Embase, 1974) through June 16, 2021. Subsequently, a "living" auto search was created with weekly updates to identify new evidence as it became available.
STUDY SELECTION
Phase 3 randomized clinical trials (RCTs) assessing first-line treatment options for mCSPC.
DATA EXTRACTION AND SYNTHESIS
Two independent reviewers extracted data from eligible RCTs. The comparative effectiveness of different treatment options was assessed with a fixed-effect network meta-analysis. Data were analyzed on July 10, 2022.
MAIN OUTCOMES AND MEASURES
Outcomes of interest included overall survival (OS), progression-free survival (PFS), grade 3 or higher adverse events, and health-related quality of life.
RESULTS
This report included 10 RCTs with 11 043 patients and 9 unique treatment groups. Median ages of the included population ranged from 63 to 70 years. Current evidence for the overall population suggests that the darolutamide (DARO) triplet (DARO + docetaxel [D] + androgen deprivation therapy [ADT]; hazard ratio [HR], 0.68; 95% CI, 0.57-0.81), as well as the abiraterone (AAP) triplet (AAP + D + ADT; HR, 0.75; 95% CI, 0.59-0.95), are associated with improved OS compared with D doublet (D + ADT) but not compared with API doublets. Among patients with high-volume disease, AAP + D + ADT may improve OS compared with D + ADT (HR, 0.72; 95% CI, 0.55-0.95) but not compared with AAP + ADT, enzalutamide (E) + ADT, and apalutamide (APA) + ADT. For patients with low-volume disease, AAP + D + ADT may not improve OS compared with APA + ADT, AAP + ADT, E + ADT, and D + ADT.
CONCLUSIONS AND RELEVANCE
The potential benefit observed with triplet therapy must be interpreted with careful accounting for the volume of disease and the choice of doublet comparisons used in the clinical trials. These findings suggest an equipoise to how triplet regimens compare with API doublet combinations and provide direction for future clinical trials.
Topics: Aged; Humans; Male; Middle Aged; Androgen Antagonists; Androgens; Castration; Network Meta-Analysis; Prostatic Neoplasms; Quality of Life
PubMed: 36862387
DOI: 10.1001/jamaoncol.2022.7762 -
International Journal of Molecular... Jan 2023Taste and smell disorders (TSDs) are common side effects in patients undergoing cancer treatments. Knowing which treatments specifically cause them is crucial to improve... (Review)
Review
Taste and smell disorders (TSDs) are common side effects in patients undergoing cancer treatments. Knowing which treatments specifically cause them is crucial to improve patients' quality of life. This review looked at the oncological treatments that cause taste and smell alterations and their time of onset. We performed an integrative rapid review. The PubMed, PROSPERO, and Web of Science databases were searched in November 2022. The article screening and study selection were conducted independently by two reviewers. Data were analyzed narratively. Fourteen studies met the inclusion criteria and were included. A high heterogeneity was detected. Taste disorders ranged between 17 and 86%, while dysosmia ranged between 8 and 45%. Docetaxel, paclitaxel, nab-paclitaxel, capecitabine, cyclophosphamide, epirubicin, anthracyclines, and oral 5-FU analogues were found to be the drugs most frequently associated with TSDs. This review identifies the cancer treatments that mainly lead to taste and smell changes and provides evidence for wider studies, including those focusing on prevention. Further studies are warranted to make conclusive indication possible.
Topics: Humans; Neoplasms; Olfaction Disorders; Quality of Life; Smell; Taste; Taste Disorders
PubMed: 36768861
DOI: 10.3390/ijms24032538 -
Annals of Translational Medicine Dec 2022The present standard treatment rarely allows the complete removal of glioblastoma (GBM). So postoperative treatments are provided to prevent or delay tumor recurrence....
BACKGROUND
The present standard treatment rarely allows the complete removal of glioblastoma (GBM). So postoperative treatments are provided to prevent or delay tumor recurrence. The overall survival (OS) rate and safety of postoperative chemotherapy alone, or combined with radiotherapy (RT), or programmed cell death-1 (PD-1) inhibitor in GBM is still unclear. The present goal was to explore postoperative treatment's effect on the survival and safety of patients with GBM.
METHODS
We searched the mainstream online databases for clinical studies of RT and chemotherapy and PD-1 inhibitors in the treatment of GBM published up to May 2020. The patients in the experimental group accepted an anti-PD-1 drug alone and RT + chemotherapy, whereas the controlled patients were treated with docetaxel alone. The literature qualities were assessed using Cochrane Risk of Bias 2.0, and studies were assigned. The meta-analysis was conducted by RevMan 5.4 software.
RESULTS
A total of 927 articles were identified through the online database search. The articles unable to meet the inclusion criteria were excluded leaving 6 studies for inclusion in the study. Compared with docetaxel-based chemotherapy for GBM, combined RT chemotherapy and PD-1 inhibitor therapy had better OS [mean difference (MD), -1.75; 95% confidence interval (CI): -2.99 to -0.51; P=0.006] and progression-free survival (PFS) and a lower incidence of adverse reactions (MD, -7.03; 95% CI: -7.64 to -6.42; P<0.00001) above grade III.
CONCLUSIONS
Postoperative combination of RT and chemotherapy and PD-1 inhibitors had some advantages over docetaxel in terms of effectiveness. More clinical trials are needed to confirm effectiveness.
PubMed: 36660707
DOI: 10.21037/atm-22-2670 -
Journal of Comparative Effectiveness... Feb 2023In the absence of head-to-head trials comparing immunotherapies for advanced nonsquamous non-small-cell lung cancer (NsqNSCLC), a network meta-analysis (NMA) was... (Meta-Analysis)
Meta-Analysis Review
In the absence of head-to-head trials comparing immunotherapies for advanced nonsquamous non-small-cell lung cancer (NsqNSCLC), a network meta-analysis (NMA) was conducted to compare the relative efficacy of these treatments. A systematic literature review of randomized controlled trials evaluating first-line-to-progression and second-line treatments for advanced NsqNSCLC informed Bayesian NMAs for overall survival (OS) and progression-free survival (PFS) end points. Among first-line-to-progression treatments, pembrolizumab + pemetrexed + platinum showed the greatest OS benefit versus other regimens and a PFS benefit versus all but three regimens. Among second-line treatments, an OS benefit was seen for atezolizumab, nivolumab and pembrolizumab versus docetaxel. Pembrolizumab + pemetrexed + platinum showed the maximum OS benefit in the first-line setting. In the second-line setting, anti-PD-1/anti-PD-L1 monotherapies were better than docetaxel.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Docetaxel; Pemetrexed; Network Meta-Analysis; Platinum; Bayes Theorem; Immunotherapy; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36621905
DOI: 10.2217/cer-2022-0016 -
Current Oncology (Toronto, Ont.) Dec 2022In recent years, significant changes have occurred in metastatic hormone-sensitive prostate cancer (mHSPC) management, where docetaxel and new androgen receptor pathway... (Meta-Analysis)
Meta-Analysis
Addition of New Androgen Receptor Pathway Inhibitors to Docetaxel and Androgen Deprivation Therapy in Metastatic Hormone-Sensitive Prostate Cancer: A Systematic Review and Metanalysis.
In recent years, significant changes have occurred in metastatic hormone-sensitive prostate cancer (mHSPC) management, where docetaxel and new androgen receptor pathway inhibitors (ARPI) have been shown to improve overall survival (OS) compared to androgen deprivation therapy (ADT). Recent data could once again radically change mHSPC treatment. PEACE-1 and ARASENS trials demonstrated a survival benefit of the addition of ARPI to docetaxel and ADT combination (triplet therapy), compared to docetaxel and ADT. With multiple options to choose from, it is crucial to identify the patients who would benefit most from triplet therapy. In this meta-analysis, we evaluated the activity of the triplet therapy versus docetaxel plus ADT in mHSPC. A systematic review of PubMed/Medline, Embase, and the proceedings of major international meetings was performed. Five RCTs fulfilled the inclusion criteria. PEACE-1 and ARASENS studies reported disease-free survival (DFS) and OS. Post hoc analysis of three other trials evaluated the combination of ARPI, docetaxel and ADT. Globally, 2538 patients were included (1270 triplet therapy; 1268 docetaxel + ADT). Triplet therapy was associated with improved OS (hazard ratio (HR) 0.74; 95% confidence interval (CI), 0.66-0.83, < 0.00001). A statistically significant benefit was shown in high-volume mHSPC patients (HR 0.76; 95% CI 0.59-0.97, = 0.03) and in patients with de novo metastatic disease (HR 0.73; 95% CI, 0.64-0.82, < 0.00001). The addition of ARPI to standard therapy was associated with DFS improvement (HR 0.41; 95% CI, 0.35-0.49, < 0.00001). This metanalysis shows a significant OS benefit from concomitant administration of ARPI, docetaxel and ADT in high volume and de novo mHSPC.
Topics: Humans; Male; Androgens; Docetaxel; Prostatic Neoplasms; Androgen Receptor Antagonists; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36547161
DOI: 10.3390/curroncol29120747