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PloS One 2024Current treatment recommendations for resectable or borderline pancreatic carcinoma support upfront surgery and adjuvant therapy. However, neoadjuvant therapy (NT) seems... (Meta-Analysis)
Meta-Analysis
Comparison of neoadjuvant treatment and surgery first for resectable or borderline resectable pancreatic carcinoma: A systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
Current treatment recommendations for resectable or borderline pancreatic carcinoma support upfront surgery and adjuvant therapy. However, neoadjuvant therapy (NT) seems to increase prognosis of pancreatic carcinoma and come to everyone's attention gradually. Randomized controlled trials offering comparison with the NT are lacking and optimal neoadjuvant treatment regimen still remains uncertain. This study aims to compare both treatment strategies for resectable or borderline resectable pancreatic cancer.
METHODS
The PRISMA checklist was used as a guide to systematically review relevant peer-reviewed literature reporting primary data analysis. We searched PubMed, Medline, EMBASE, Cochrane Datebase and related reviews for randomized controlled trials comparing neoadjuvant therapy with surgery first for resectable or borderline resectable pancreatic carcinoma. We estimated relative hazard ratios (HRs) for median overall survival and ratios risks (RRs) for microscopically complete (R0) resection among different neoadjuvant regimens and major complications. We assessed the effects of neoadjuvant therapy on R0 resection rate and median overall survival with Bayesian analysis.
RESULTS
Thirteen eligible articles were included. Eight studies performed comparison neoadjuvant therapy with surgery first, and R0 resection rate was recorded in seven studies. Compared with surgery first, neoadjuvant therapy did increase the R0 resection rate (RR = 1.53, I2 = 0%, P< 0.00001), there was a certain possibility that gemcitabine + cisplatin (Gem+Cis) + Radiotherapy was the most favorable in terms of the fact that there was no significant difference concerning the results from the individual studies. In direct comparison, four studies were included and estimated that Neoadjuvant therapy improved mOS compared with upfront surgery (HR 0.68, 95% CI 0.58-0.92; P = 0.012; I2 = 15%), after Bayesian analysis it seemed that regimen with Cisplatin/ Epirubicin then Gemcitabine/ Capecitabine (PEXG) was most likely the best with a relatively small sample size. The rate of major surgical complications was available for six studies and ranged from 11% to 56% with neoadjuvant therapy and 11% to 45% with surgery first. There was no significant difference between neoadjuvant therapy and surgery first, also with a high heterogeneity (RR = 0.96, 95%CI = 0.65-1.43; P = 0.85; I2 = 46%).
CONCLUSION
In conclusion neoadjuvant therapy might offer benefit over up-front surgery. Neoadjuvant therapy increased the R0 resection rate with gemcitabine + cisplatin + Radiotherapy that was the most favorable and improved mOS with Cisplatin/ Epirubicin then Gemcitabine/ Capecitabine (PEXG) that was most likely the best.
Topics: Humans; Neoadjuvant Therapy; Gemcitabine; Capecitabine; Cisplatin; Epirubicin; Network Meta-Analysis; Bayes Theorem; Randomized Controlled Trials as Topic; Pancreatic Neoplasms; Deoxycytidine; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38451955
DOI: 10.1371/journal.pone.0295983 -
Medicine Nov 2023There have been controversial findings from recent studies regarding anthracyclines use and the subsequent risk of arrhythmias. This study aimed to evaluate the existing... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There have been controversial findings from recent studies regarding anthracyclines use and the subsequent risk of arrhythmias. This study aimed to evaluate the existing evidence of the risk of arrhythmias in patients treated with anthracyclines.
METHODS
PubMed, Scopus, and Web of Science databases were searched up to April 2022 using keywords such as "anthracycline" and "arrhythmia." Dichotomous data were presented as relative risk (RR) and confidence interval (CI), while continuous data were presented as mean difference (MD) and CI. Revman software version 5.4 was used for the analysis.
RESULTS
Thirteen studies were included with a total of 26891 subjects. Pooled analysis showed that anthracyclines therapy was significantly associated with a higher risk of arrhythmia (RR: 1.58; 95% CI: 1.41-1.76; P < .00001), ST segment and T wave abnormalities (RR: 1.73, 95% CI: 1.18-2.55, P = .005), conduction abnormalities and AV block (RR = 1.86, 95% CI = 1.06-3.25, P = .03), and tachycardia (RR: 1.736, 95% CI: 1.11-2.69, P = .02). Further analyses of the associations between anthracyclines and atrial flutter (RR = 1.30, 95% CI = 0.29-5.89, P = .74), atrial ectopic beats (RR: 1.27, 95% CI: 0.78-2.05, P = .34), and ventricular ectopic beats (RR: 0.93, 95% CI: 0.53-1.65, P = .81) showed no statistically significant results. Higher doses of anthracycline were associated with a higher risk of arrhythmias (RR: 1.49; 95% CI: 1.08-2.05; P = .02) compared to the lower doses (RR: 1.36; 95% CI: 1.00-1.85; P = .05). Newer generations of Anthracycline maintained the arrhythmogenic properties of previous generations, such as Doxorubicin.
CONCLUSION
Anthracyclines therapy was significantly associated with an increased risk of arrhythmias. Accordingly, Patients treated with anthracyclines should be screened for ECG abnormalities and these drugs should be avoided in patients susceptible to arrhythmia. The potential benefit of the administration of prophylactic anti-fibrotic and anti-arrhythmic drugs should also be explored.
Topics: Humans; Anthracyclines; Arrhythmias, Cardiac; Antibiotics, Antineoplastic; Doxorubicin; Tachycardia; Leukemia, Myeloid, Acute
PubMed: 37986405
DOI: 10.1097/MD.0000000000035770 -
European Journal of Surgical Oncology :... Dec 2023PIPAC consists in delivering normothermic chemotherapy solution directly into the peritoneal cavity as an aerosol under pressure. Currently PIPAC is considered as a... (Review)
Review
BACKGROUND
PIPAC consists in delivering normothermic chemotherapy solution directly into the peritoneal cavity as an aerosol under pressure. Currently PIPAC is considered as a palliative treatment for patients suffering from non-resectable peritoneal carcinomatosis. We performed a SR to assess tolerance and response of this novel method among patient with OC.
METHODS
We searched electronic database PubMed, Embase, Web of Science, Clinical Trials.gov. We only included clinical studies reporting PIPAC with cisplatin and doxorubicin in patients with ovarian cancer.
RESULTS
This systematic review included 4 studies. In 3 studies all patients were pretreated with cytoreductive surgery, in 1 study surgery was performed in 8/34 (23 %) patients. Mean PCI at first PIPAC procedure ranged from 16.3 to 19.6. All studies reported the proportion of patients with ascites at the first PIPAC with a pooled rate of 48,3 %. Pooled rate of CTCAE Grade 3 toxicity calculated on the total number of PIPAC was 6 % and Grade 4 was 0.9 %. One study reported two cases of small bowel perforation related or potentially related to PIPAC. On study reported a cumulative survival after 400 days of 62 % and a mean actuarial survival time of all patients who underwent PIPAC of 442 days. In another study the mean time to progression was 144 days (95 % CI 122-168 days).
CONCLUSION
This systematic review demonstrated that PIPAC with cisplatin and doxorubicin appear to have a good safety profile with low toxicity and encouraging trend in terms of overall survival.
Topics: Humans; Female; Cisplatin; Percutaneous Coronary Intervention; Antineoplastic Combined Chemotherapy Protocols; Ovarian Neoplasms; Doxorubicin; Aerosols
PubMed: 37951158
DOI: 10.1016/j.ejso.2023.107250 -
Advances in Clinical and Experimental... May 2024Osteosarcoma is a pleomorphic cancer that frequently affects children and teenagers. Although several chemotherapy regimens have been utilized for many years, the best... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osteosarcoma is a pleomorphic cancer that frequently affects children and teenagers. Although several chemotherapy regimens have been utilized for many years, the best therapeutic option for the treatment of osteosarcoma has not yet been determined.
OBJECTIVES
This meta-analysis was designed to assess the clinical efficacy of a high-dose methotrexate, doxorubicin and cisplatin (MAP) regimen and compare its survival outcomes with those of other chemotherapy strategies in patients diagnosed with osteosarcoma.
MATERIAL AND METHODS
We systematically searched databases, namely Embase, the Cochrane Library and PubMed, up to August 2022, for relevant studies investigating the impact of the MAP chemotherapy protocol on survival among patients with osteosarcoma. The odds ratio (OR) pooled estimates and their 95% confidence intervals (95% CIs) were calculated.
RESULTS
Twelve studies including 4102 patients were eligible for analysis in this study. The estimated pooled ORs of the 3-year overall survival (OS) and event-free survival (EFS) were OR = 1.08 (95% CI: 0.72-1.62, p = 0.70) and OR = 1.04 (95% CI: 0.81-1.32, p = 0.78, respectively). The 5-year OS and EFS were OR = 0.87 (95% CI: 0.62-1.23, p = 0.42) and OR = 1.13 (95% CI: 0.76-1.68, p = 0.54), respectively, with no statistical differences. The subgroup analysis of MAP compared to a 2-drug regimen (doxorubicin and cisplatin) revealed a significant difference between the 2 chemotherapy strategy groups in 3-year OS rates (OR = 0.72 (95% CI: 0.56-0.92, p = 0.009)) and 5-year EFS rates (OR = 0.57 (95% CI: 0.43-0.76, p < 0.001)).
CONCLUSION
The MAP chemotherapy strategy for osteosarcoma showed superiority over other regimens, especially over the 2-drug regimen (doxorubicin/cisplatin), in terms of better prognosis and safety.
Topics: Osteosarcoma; Humans; Cisplatin; Doxorubicin; Bone Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Methotrexate; Treatment Outcome; Antineoplastic Agents
PubMed: 37747442
DOI: 10.17219/acem/170098 -
Medicine Aug 2023Novel-fosfamides (NFOs) belong to active metabolites of ifosfamide that bypass the generation of toxic byproducts. In this analysis, we aimed to comprehensively assess... (Meta-Analysis)
Meta-Analysis
Novel-fosfamide monotherapy or in combination with doxorubicin versus doxorubicin alone in patients with advanced soft tissue sarcoma: A pooled analysis of randomized clinical trials.
BACKGROUND
Novel-fosfamides (NFOs) belong to active metabolites of ifosfamide that bypass the generation of toxic byproducts. In this analysis, we aimed to comprehensively assess the benefits and risks of NFO monotherapy or in combination with doxorubicin (DOX) versus single-drug DOX in previously untreated patients with advanced soft-tissue sarcoma (ASTS).
METHODS
Online PubMed, Web of Science, Embase, and Cochrane CENTRAL databases were systematically searched on April 26, 2022. Objective response rate and disease control rate were primary outcomes. Overall survival (OS), progression-free survival (PFS), and grade ≥ 3 treatment-related adverse events were secondary outcomes.
RESULTS
In all, 3 randomized clinical trials with a total of 1207 ASTS patients were eligible. DOX plus NFO combination therapy showed higher risk ratios of objective response rate (1.50, 95% CI 1.20-1.68, P = .0003) and disease control rate (1.15, 95% CI 1.05-1.27, P = .0030) compared with DOX monotherapy. Nevertheless, NFO-based monotherapy and combination therapy were found no improvements on OS (hazard ratio 0.93, 95% CI 0.52-1.65, P = .8050) and PFS (hazard ratio 0.88, 95% CI 0.54-1.43, P = .6088) against DOX. More incidences of grade 3 or worse anemia, thrombocytopenia, stomatitis, diarrhea, constipation, and febrile neutropenia were observed in NFO-based treatments.
CONCLUSION
Adding NFO to DOX as first-line therapy improved the responses in ASTS patients but did not prolong OS and PFS. Grade 3 or worse treatment-related adverse events should be treated with caution during the NFO-based therapies.
Topics: Humans; Randomized Controlled Trials as Topic; Doxorubicin; Soft Tissue Neoplasms; Sarcoma; Thrombocytopenia
PubMed: 37603507
DOI: 10.1097/MD.0000000000034902 -
World Journal of Urology Aug 2023The present systematic review and network meta-analysis (NMA) compared the current different neoadjuvant chemotherapy (NAC) regimes for bladder cancer patients to rank... (Meta-Analysis)
Meta-Analysis
Comparison between different neoadjuvant chemotherapy regimens and local therapy alone for bladder cancer: a systematic review and network meta-analysis of oncologic outcomes.
PURPOSE
The present systematic review and network meta-analysis (NMA) compared the current different neoadjuvant chemotherapy (NAC) regimes for bladder cancer patients to rank them.
METHODS
We used the Bayesian approach in NMA of six different therapy regimens cisplatin, cisplatin/doxorubicin, (gemcitabine/cisplatin) GC, cisplatin/methotrexate, methotrexate, cisplatin, and vinblastine (MCV) and (MVAC) compared to locoregional treatment.
RESULTS
Fifteen studies comprised 4276 patients who met the eligibility criteria. Six different regimes were not significantly associated with a lower likelihood of overall mortality rate compared to local treatment alone. In progression-free survival (PFS) rates, cisplatin, GC, cisplatin/methotrexate, MCV and MVAC were not significantly associated with a higher likelihood of PFS rate compared to locoregional treatment alone. In local control outcome, MCV, MVAC, GC and cisplatin/methotrexate were not significantly associated with a higher likelihood of local control rate versus locoregional treatment alone. Nevertheless, based on the analyses of the treatment ranking according to SUCRA, it was highly likely that MVAC with high certainty of results appeared as the most effective approach in terms of mortality, PFS and local control rates. GC and cisplatin/doxorubicin with low certainty of results was found to be the best second options.
CONCLUSION
No significant differences were observed in mortality, progression-free survival and local control rates before and after adjusting the type of definitive treatment in any of the six study arms. However, MVAC was found to be the most effective regimen with high certainty, while cisplatin alone and cisplatin/methotrexate should not be recommended as a neoadjuvant chemotherapy regime.
Topics: Humans; Cisplatin; Neoadjuvant Therapy; Methotrexate; Bayes Theorem; Network Meta-Analysis; Gemcitabine; Antineoplastic Combined Chemotherapy Protocols; Urinary Bladder Neoplasms; Doxorubicin; Vinblastine; Cystectomy
PubMed: 37347252
DOI: 10.1007/s00345-023-04478-w -
Oncogene Jan 2023Over the last 40 years osteosarcoma (OS) survival has stagnated with patients commonly resistant to neoadjuvant MAP chemotherapy involving high dose methotrexate,...
Over the last 40 years osteosarcoma (OS) survival has stagnated with patients commonly resistant to neoadjuvant MAP chemotherapy involving high dose methotrexate, adriamycin (doxorubicin) and platinum (cisplatin). Due to the rarity of OS, the generation of relevant cell models as tools for drug discovery is paramount to tackling this issue. Four literature databases were systematically searched using pre-determined search terms to identify MAP resistant OS cell lines and patients. Drug exposure strategies used to develop cell models of resistance and the impact of these on the differential expression of resistance associated genes, proteins and non-coding RNAs are reported. A comparison to clinical studies in relation to chemotherapy response, relapse and metastasis was then made. The search retrieved 1891 papers of which 52 were relevant. Commonly, cell lines were derived from Caucasian patients with epithelial or fibroblastic subtypes. The strategy for model development varied with most opting for continuous over pulsed chemotherapy exposure. A diverse resistance level was observed between models (2.2-338 fold) with 63% of models exceeding clinically reported resistance levels which may affect the expression of chemoresistance factors. In vitro p-glycoprotein overexpression is a key resistance mechanism; however, from the available literature to date this does not translate to innate resistance in patients. The selection of models with a lower fold resistance may better reflect the clinical situation. A comparison of standardised strategies in models and variants should be performed to determine their impact on resistance markers. Clinical studies are required to determine the impact of resistance markers identified in vitro in poor responders to MAP treatment, specifically with respect to innate and acquired resistance. A shift from seeking disputed and undruggable mechanisms to clinically relevant resistance mechanisms may identify key resistance markers that can be targeted for patient benefit after a 40-year wait.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Clinical Relevance; Doxorubicin; Neoplasm Recurrence, Local; Osteosarcoma; Drug Resistance, Neoplasm
PubMed: 36434179
DOI: 10.1038/s41388-022-02529-x -
Medical Archives (Sarajevo, Bosnia and... Jun 2022Bladder cancer is still a burden on the world of oncology medicine, which every year affects about 3.4 million people globally with 430,000 new cases per year. It is the... (Meta-Analysis)
Meta-Analysis
Comparison Between Intravesical Chemotherapy Epirubicin and Mitomycin-C after TURB vs TURB Alone With Recurrence Rate of Non-Muscle Invasive Bladder Cancer: Meta-Analysis.
BACKGROUND
Bladder cancer is still a burden on the world of oncology medicine, which every year affects about 3.4 million people globally with 430,000 new cases per year. It is the fourth most common cancer in men and eighth most common women malignancy in the world. This makes bladder cancer a "silent killer" and it needs appropriate treatment planning. Single immediate instillation of chemotherapy after transurethral resection of the bladder (TURB) is recommended by EAU guideline, but its use remains a controversy.
OBJECTIVE
Study aimed to analyze benefit of intravesical chemotherapy following TURB in terms of recurrency of non-muscle invasive bladder cancer (NMIBC).
METHODS
Systematic review and meta-analysis of randomized controlled trials comparing the efficacy of a single instillation after TURB with TURB alone in NMIBC (pTa-pT1) patients was conducted. Studies searched throughout Medline, PubMed, Embase, and Cochrane in December 2018. Keywords were intravesical chemotherapy, combination, transurethral resection, bladder cancer. Inclusion criteria were RCT studies, subjects in study were treated single immediate chemotherapy instillation after TURB compared to TURB alone in patient with pTa-pT1 urothelial carcinoma of the bladder. Trials with additional treatment prior to first reccurence were not eligible. Studies using recurrence rate as dependent variable. From 361 studies, in total 11 studies were eligible for this meta-analysis.
RESULTS
From those 11 studies, it is shown that intravesical chemotherapy using Epirubicin and Mitomycin-C following TURB showed significant decrease of recurrence rate of bladder cancer even to progression of the disease compared to TURB alone (p<0.05) with pooled Risk Ratio were 0.69 and pooled heterogeneity (I) were 26.6%.
CONCLUSION
This meta-analysis study showed that combination therapy of intravesical chemotherapy after TURB is superior to TURB alone in showing the recurrence rate of NMIBC.
Topics: Administration, Intravesical; Carcinoma, Transitional Cell; Epirubicin; Female; Humans; Male; Mitomycin; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Urinary Bladder Neoplasms
PubMed: 36200115
DOI: 10.5455/medarh.2022.76.198-201 -
Medicine Sep 2022Double-expressor lymphoma (DEL) is associated with a poor prognosis. The standard treatment for patients with DEL remains controversial. A comparison of the safety and... (Meta-Analysis)
Meta-Analysis
PURPOSE
Double-expressor lymphoma (DEL) is associated with a poor prognosis. The standard treatment for patients with DEL remains controversial. A comparison of the safety and feasibility of R-CHOP and DA-EPOCH-R as the first-line therapy for patients with DEL is urgently needed.
METHODS
The clinical and treatment outcomes of 75 DEL patients were retrospectively analyzed. The role of DA-EPOCH-R was determined and compared to that of R-CHOP in DEL patients. PubMed, Embase, the Cochrane Central Library, and ClinicalTrials.gov were systematically searched up to November 1, 2021 and were evaluated by Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Articles comparing DA-EPOCH-R versus R-CHOP in patients with DEL were included.
RESULTS
Overall, 49 and 26 DEL patients received R-CHOP and DA-EPOCH-R, respectively. Although the difference in response for patients who received R-CHOP and DA-EPOCH-R was not significant (P = .347), DA-EPOCH-R may improve the prognosis compared to R-CHOP (P = .056 for progression-free survival [PFS], P = .009 for overall survival [OS]). A systematic review and meta-analysis including 412 DEL patients in six articles were conducted. The event rate for 3-year PFS was significantly lower in patients receiving DA-EPOCH-R treatment than in those undergoing R-CHOP treatment (OR = 0.63, 95% CI = 0.42-0.94, P = .02), whereas no statistically significant difference was found in the HRs for both PFS and OS or the event rate for 3-year OS.
CONCLUSION
The results of this study indicated that DA-EPOCH-R might improve the prognosis of DEL patients compared with R-CHOP.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Etoposide; Humans; Lymphoma, Large B-Cell, Diffuse; Prednisone; Prognosis; Retrospective Studies; Rituximab; Vincristine
PubMed: 36197215
DOI: 10.1097/MD.0000000000030620 -
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