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Frontiers in Oncology 2021Neoadjuvant chemotherapy has been accepted as an effective curative treatment for muscle-invasive bladder cancer patients and has resulted in better survival outcomes...
Curative Effect and Survival Assessment Comparing Gemcitabine and Cisplatin Versus Methotrexate, Vinblastine, Doxorubicin and Cisplatin as Neoadjuvant Therapy for Bladder Cancer: A Systematic Review and Meta-Analysis.
BACKGROUND
Neoadjuvant chemotherapy has been accepted as an effective curative treatment for muscle-invasive bladder cancer patients and has resulted in better survival outcomes than radical cystectomy or a cisplatin-based regimen. In the present study, we aimed to compare the two most commonly used cisplatin-based neoadjuvant chemotherapies, gemcitabine plus cisplatin and methotrexate plus vinblastine plus doxorubicin plus cisplatin, by summarizing and analyzing clinical data and outcomes of published research.
METHODS
We searched for qualified studies that compared these two types of neoadjuvant chemotherapy, including 4 randomized controlled trials and 14 retrospective studies. Data and information on pathological responses and long-term survival studies were extracted and analyzed separately.
RESULTS
A total of 18 studies with 3116 patients were selected from 1188 studies, which contained data on pathological complete response, pathological partial response, and overall survival. In contrast to the results of previous studies, there was no significant difference in pathological complete response (odds ratio, 0.97; 95% confidence interval, 0.81-1.15), pathological partial response (odds ratio, 0.85; 95% confidence interval, 0.72-1.14), and overall survival (hazard ratio, 0.99; 95% confidence interval, 0.83-1.17) between GC and MVAC in this meta-analysis.
CONCLUSION
No significant differences were observed between GC and MVAC in the muscle-invasive bladder cancer treatment due to the similar curative effect and parallel long survival outcomes due to the similar curative effect and parallel long survival outcomes. The priority selection of GC or MVAC in the clinic should be guided by further investigation, and the clinical standard strategy still counts on the results of more randomized controlled trials in the future.
PubMed: 34900663
DOI: 10.3389/fonc.2021.678896 -
European Journal of Cancer (Oxford,... Mar 2022Cancer in neonates and infants is a rare but challenging entity. Treatment is complicated by marked physiological changes during the first year of life, excess rates of... (Review)
Review
Cancer in neonates and infants is a rare but challenging entity. Treatment is complicated by marked physiological changes during the first year of life, excess rates of toxicity, mortality, and late effects. Dose optimisation of chemotherapeutics may be an important step to improving outcomes. Body size-based dosing is used for most anticancer drugs used in infants. However, dose regimens are generally not evidence based, and dosing strategies are frequently inconsistent between tumour types and treatment protocols. In this review, we collate available pharmacological evidence supporting dosing regimens in infants for a wide range of cytotoxic drugs. A systematic review was conducted, and available data ranked by a level of evidence (1-5) and a grade of recommendation (A-D) provided on a consensus basis, with recommended dosing approaches indicated as appropriate. For 9 of 29 drugs (busulfan, carboplatin, cyclophosphamide, daunorubicin, etoposide, fludarabine, isotretinoin, melphalan and vincristine), grade A was scored, indicating sufficient pharmacological evidence to recommend a dosing algorithm for infants. For busulfan and carboplatin, sufficient data were available to recommend therapeutic drug monitoring in infants. For eight drugs (actinomycin D, blinatumomab, dinutuximab, doxorubicin, mercaptopurine, pegaspargase, thioguanine and topotecan), some pharmacological evidence was available to guide dosing (graded as B). For the remaining drugs, including commonly used agents such as cisplatin, cytarabine, ifosfamide, and methotrexate, pharmacological evidence for dosing in infants was limited or non-existent: grades C and D were scored for 10 and 2 drugs, respectively. The review provides clinically relevant evidence-based dosing guidance for cytotoxic drugs in neonates and infants.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Carboplatin; Etoposide; Humans; Infant; Infant, Newborn
PubMed: 34865945
DOI: 10.1016/j.ejca.2021.11.001 -
Molecules (Basel, Switzerland) Oct 2021Zeolites and zeolitic imidazolate frameworks (ZIFs) are widely studied as drug carrying nanoplatforms to enhance the specificity and efficacy of traditional anticancer...
Zeolites and zeolitic imidazolate frameworks (ZIFs) are widely studied as drug carrying nanoplatforms to enhance the specificity and efficacy of traditional anticancer drugs. At present, there is no other systematic review that assesses the potency of zeolites/ZIFs as anticancer drug carriers. Due to the porous nature and inherent pH-sensitive properties of zeolites/ZIFs, the compounds can entrap and selectively release anticancer drugs into the acidic tumor microenvironment. Therefore, it is valuable to provide a comprehensive overview of available evidence on the topic to identify the benefits of the compound as well as potential gaps in knowledge. The purpose of this study was to evaluate the potential therapeutic applications of zeolites/ZIFs as drug delivery systems delivering doxorubicin (DOX), 5-fluorouracil (5-FU), curcumin, cisplatin, and miR-34a. Following PRISMA guidelines, an exhaustive search of PubMed, Scopus, Embase, and Web of Science was conducted. No language or time limitations were used up to 25th August 2021. Only full text articles were selected that pertained to the usage of zeolites/ZIFs in delivering anticancer drugs. Initially, 1279 studies were identified, of which 572 duplicate records were excluded. After screening for the title, abstract, and full texts, 53 articles remained and were included in the qualitative synthesis. An Inter-Rater Reliability (IRR) test, which included a percent user agreement and reliability percent, was conducted for the 53 articles. The included studies suggest that anticancer drug-incorporated zeolites/ZIFs can be used as alternative treatment options to enhance the efficacy of cancer treatment by mitigating the drawbacks of drugs under conventional treatment.
Topics: Animals; Antineoplastic Agents; Doxorubicin; Drug Carriers; Drug Delivery Systems; Female; Humans; Hydrogen-Ion Concentration; Male; Nanoparticles; Neoplasms; Porosity; Tumor Cells, Cultured; Tumor Microenvironment; Zeolites
PubMed: 34684777
DOI: 10.3390/molecules26206196 -
Journal of the American Heart... Sep 2021Background Physical exercise is an intervention that might protect against doxorubicin-induced cardiotoxicity. In this meta-analysis and systematic review, we aimed to... (Meta-Analysis)
Meta-Analysis
Background Physical exercise is an intervention that might protect against doxorubicin-induced cardiotoxicity. In this meta-analysis and systematic review, we aimed to estimate the effect of exercise on doxorubicin-induced cardiotoxicity and to evaluate mechanisms underlying exercise-mediated cardioprotection using (pre)clinical evidence. Methods and Results We conducted a systematic search in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Cochrane's and Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tools were used to assess the validity of human and animal studies, respectively. Cardiotoxicity outcomes reported by ≥3 studies were pooled and structured around the type of exercise intervention. Forty articles were included, of which 3 were clinical studies. Overall, in humans (sample sizes ranging from 24 to 61), results were indicative of exercise-mediated cardioprotection, yet they were not sufficient to establish whether physical exercise protects against doxorubicin-induced cardiotoxicity. In animal studies (n=37), a pooled analysis demonstrated that forced exercise interventions significantly mitigated in vivo and ex vivo doxorubicin-induced cardiotoxicity compared with nonexercised controls. Similar yet slightly smaller effects were found for voluntary exercise interventions. We identified oxidative stress and related pathways, and less doxorubicin accumulation as mechanisms underlying exercise-induced cardioprotection, of which the latter could act as an overarching mechanism. Conclusions Animal studies indicate that various exercise interventions can protect against doxorubicin-induced cardiotoxicity in rodents. Less doxorubicin accumulation in cardiac tissue could be a key underlying mechanism. Given the preclinical evidence and limited availability of clinical data, larger and methodologically rigorous clinical studies are needed to clarify the role of physical exercise in preventing cardiotoxicity in patients with cancer. Registration URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42019118218.
Topics: Animals; Antibiotics, Antineoplastic; Cardiotoxicity; Doxorubicin; Exercise; Humans
PubMed: 34472371
DOI: 10.1161/JAHA.121.021580 -
Oxidative Medicine and Cellular... 2021Although doxorubicin chemotherapeutic drug is commonly used to treat various solid and hematological tumors, its clinical use is restricted because of its adverse...
A Systematic Review of the Potential Chemoprotective Effects of Resveratrol on Doxorubicin-Induced Cardiotoxicity: Focus on the Antioxidant, Antiapoptotic, and Anti-Inflammatory Activities.
PURPOSE
Although doxorubicin chemotherapeutic drug is commonly used to treat various solid and hematological tumors, its clinical use is restricted because of its adverse effects on the normal cells/tissues, especially cardiotoxicity. The use of resveratrol may mitigate the doxorubicin-induced cardiotoxic effects. For this aim, we systematically reviewed the potential chemoprotective effects of resveratrol against the doxorubicin-induced cardiotoxicity.
METHODS
In the current study, a systematic search was performed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline for the identification of all relevant studies on "the role of resveratrol on doxorubicin-induced cardiotoxicity" in the electronic databases of Web of Science, PubMed, and Scopus up to March 2021 using search terms in their titles and abstracts. Two hundred and eighteen articles were screened in accordance with a predefined set of inclusion and exclusion criteria. Finally, 33 eligible articles were included in this systematic review.
RESULTS
The and findings demonstrated a decreased cell survival, increased mortality, decreased heart weight, and increased ascites in the doxorubicin-treated groups compared to the control groups. The combined treatment of resveratrol and doxorubicin showed an opposite pattern than the doxorubicin-treated groups alone. Furthermore, this chemotherapeutic agent induced the biochemical and histopathological changes on the cardiac cells/tissue; however, the results (for most of the cases) revealed that these alterations induced by doxorubicin were reversed near to normal levels (control groups) by resveratrol coadministration.
CONCLUSION
The results of this systematic review stated that coadministration of resveratrol alleviates the doxorubicin-induced cardiotoxicity. Resveratrol exerts these chemoprotective effects through several main mechanisms of antioxidant, antiapoptosis, and anti-inflammatory.
Topics: Anti-Inflammatory Agents; Antioxidants; Apoptosis; Cardiotoxicity; Doxorubicin; Humans; Resveratrol
PubMed: 34471463
DOI: 10.1155/2021/2951697 -
Medicine Aug 2021It is well known that liposome-based delivery of cytotoxic chemotherapeutics has been proposed as a putative strategy to enhance drug tolerability and efficacy compared... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It is well known that liposome-based delivery of cytotoxic chemotherapeutics has been proposed as a putative strategy to enhance drug tolerability and efficacy compared to the conventional chemotherapy. However, its potential effect on improving prognosis remains largely unknown. The current meta-analysis is to explore the prognosis of cancer patients undergoing liposomal doxorubicin-based chemotherapy.
METHODS
A detailed review of English and Chinese literature was conducted up to March 21, 2020. We evaluate its possible correlations using hazard ratios (HRs) with 95% confidence intervals (CIs). The pooled data were calculated by STATA software and Review Manager 5.3 software.
RESULTS
Consequently, 26 studies including 7943 patients were satisfied in current analysis. There were no significant differences between liposomal and conventional chemotherapy in OS (HR = 0.98, 95%CI: 0.93-1.04, P = .544) and PFS (HR = 1.00, 95%CI: 0.92-1.10, P = .945). Likewise, subgroup-analysis regarding country, cancer type, and sample sizes also showed the similar results of the 2 paired groups.
CONCLUSION
Taken together, our finding has demonstrated that there was no association of undergoing liposomal doxorubicin-based chemotherapy with cancer prognosis. However, detailed and further studies are needed to confirm our conclusion.
Topics: Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Humans; Multicenter Studies as Topic; Neoplasms; Polyethylene Glycols; Proportional Hazards Models; Randomized Controlled Trials as Topic
PubMed: 34449454
DOI: 10.1097/MD.0000000000026690 -
Cancers Jul 2021MYC/BCL2 protein co-expression (i.e., double expressor) has been shown to be a negative predictor of outcome in diffuse large B-cell lymphoma (DLBCL). We aimed to... (Review)
Review
MYC/BCL2 protein co-expression (i.e., double expressor) has been shown to be a negative predictor of outcome in diffuse large B-cell lymphoma (DLBCL). We aimed to establish the incidence of double expressor status in patients with de novo DLBCL and identify the predictive value of this biomarker on treatment response through systematic review and meta-analysis. PubMed and Embase were searched for studies published through December 2019 that reported proportions of double expressor DLBCL. The pooled proportions of MYC and BCL2 expression, both alone and in combination, were computed using the inverse variance method for calculating weights and by the DerSimonian-Laird method. The pooled odds ratios (ORs) of complete remission (CR) rate were calculated, and meta-regression analysis was conducted to explore heterogeneity. Forty-one studies (7054 patients) were included. The pooled incidence of double expressor status in DLBCL was 23% (95% confidence interval [CI], 20-26%), with an adjusted estimate of 31% (95% CI, 27-36%). Neither MYC/BCL2 protein cutoff values, race, mean, or median age of included patients, or overall study quality was a significant factor of heterogeneity ( ≥ 0.20). Cases without double expressor status demonstrated a higher probability of CR to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone treatment (OR, 2.69; 95% CI, 1.55-4.67). Our results reaffirm the predictive power of this important biomarker.
PubMed: 34282799
DOI: 10.3390/cancers13133369 -
Cancers Jun 2021Platinum-based neoadjuvant chemotherapy (NAC) is widely used for treating muscle-invasive bladder cancer (MIBC). A systematic review was performed following PRISMA... (Review)
Review
Comparison of Oncologic Outcomes of Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin (ddMVAC) with Gemcitabine and Cisplatin (GC) as Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: Systematic Review and Meta-Analysis.
Platinum-based neoadjuvant chemotherapy (NAC) is widely used for treating muscle-invasive bladder cancer (MIBC). A systematic review was performed following PRISMA guidelines. PubMed, Embase, and the Cochrane Library were searched up to December 2020. We conducted a meta-analysis to compare the oncologic outcomes of ddMVAC (dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin) and GC (gemcitabine and cisplatin), which are the most widely used NAC regimens. Endpoints included pathologic complete response (pCR), pathologic downstaging (pDS), overall survival (OS), and cancer-specific survival (CSS). Five studies, with a total of 1206 patients, were included for meta-analysis. pCR was observed in 35.2% of the ddMVAC arm and in 25.1% of the GC arm, and pCR was significantly higher in ddMVAC than in GC (odds ratio (OR), 1.45; 95% confidence interval (CI), 1.11-1.89; = 0.006). There was no significant difference in pDS (OR, 1.37; CI, 0.84-2.21; = 0.20). OS was significantly higher in ddMVAC than in GC (hazard ratio, 2.16; CI, 1.42-3.29; = 0.0004). Only one study reported CSS outcomes. The results of this analysis indicate that ddMVAC is superior to GC in terms of pCR and OS, suggesting that ddMVAC is more effective than GC in NAC for MIBC. However, this should be interpreted with caution because of the inherent limitations of retrospective studies.
PubMed: 34199565
DOI: 10.3390/cancers13112770 -
Critical Reviews in Oncology/hematology Jul 2021Doxorubicin represents the mainstay in the upfront treatment of diffuse large B-cell lymphoma (DLBCL) patients. However, its administration is sometimes hampered by the... (Meta-Analysis)
Meta-Analysis Review
Doxorubicin represents the mainstay in the upfront treatment of diffuse large B-cell lymphoma (DLBCL) patients. However, its administration is sometimes hampered by the coexistence of former comorbidities/cardiac issues, especially in the elderly population. Liposome encapsulated drug delivery systems have been adopted to reduce the exposure of normal tissues to the drug, both in solid cancers and lymphomas. Despite claims for lower toxicity, the efficacy of non-pegylated liposome doxorubicin (NPLD) in DLBCL, as compared to standard doxorubicin, has never been established. We systematically reviewed relevant literature of NPLD in lymphoma treatment. Adjusting for age/comorbidities, our metanalysis revealed that the use of combinations including NPLD (R-COMP) were non-inferior in terms of response, overall and progression-free survival to the standard of care (R-CHOP) in overlapping series of DLBCL patients. R-COMP may represent a safe and active option for elderly patients with DLBCL, or for those with some extent of cardiac impairment at baseline.
Topics: Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, Large B-Cell, Diffuse; Prednisone; Rituximab; Treatment Outcome; Vincristine
PubMed: 34087342
DOI: 10.1016/j.critrevonc.2021.103377 -
Journal of Gastrointestinal Oncology Apr 2021Gastric cancer progression resulting in metachronous peritoneal metastasizing is almost always associated with an adverse prognosis. This review discusses various... (Review)
Review
Gastric cancer progression resulting in metachronous peritoneal metastasizing is almost always associated with an adverse prognosis. This review discusses various options of preventing metachronous peritoneal metastases in radically operated gastric cancer patients. Also examined are different hyperthermic intraperitoneal chemotherapy (HIPEC) regimens employed in gastric cancer treatment, postoperative morbidity and mortality rates and long-term treatment outcomes. The authors also review their own experience of using HIPEC based on the combination of cisplatin and doxorubicin in doses of 50 mg/m at 42 °C for 1 h to prevent gastric cancer peritoneal dissemination. As a result, progression-free survival rose from 19.6%±5.6% to 47.1%±6.3% (P <0.001) and dissemination-free survival-from 22.7%±6.0% to 51.9%±6.3% (P <0.001). It is noted that the combination of the described HIPEC regimen with systemic chemotherapy helped raise metastases-free 3-year survival rate to up to 91.0%±9.0% (P =0.025) compared with 48.6%±6.4% for patients who underwent only a combined surgery/HIPEC treatment. HIPEC is a promising combined treatment strategy for radically operated gastric cancer patients that can improve patient survival and decrease peritoneal dissemination rate. However, the number of randomized studies on adjuvant HIPEC are still insufficient for a subgroup assessment of efficacy of the given chemotherapy regimens and generation of evidence-based recommendations on the individual use of chemotherapy agents and their combinations, and HIPEC procedural techniques. Further prospective randomized studies are needed to assess the practicability of complementing HIPEC with adjuvant systemic chemotherapies.
PubMed: 33968422
DOI: 10.21037/jgo-20-129