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The Journal of International Medical... Apr 2022To undertake a meta-analysis of the treatment effects of different second-line chemotherapy regimens compared with FOLFIRINOX (FOL [folinic acid], F [fluorouracil], IRIN... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To undertake a meta-analysis of the treatment effects of different second-line chemotherapy regimens compared with FOLFIRINOX (FOL [folinic acid], F [fluorouracil], IRIN [irinotecan], OX [oxaliplatin]) after failure of gemcitabine-based first-line therapy in patients with pancreatic cancer.
METHODS
This meta-analysis searched electronic databases, including Embase®, Medline, PubMed® and the Cochrane library, for eligible studies that reported the use of FOLFIRINOX and other drug regimens as second-line chemotherapy after failure of gemcitabine-based chemotherapy. Pooled analyses for progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and grade 3/4 treatment-emergent adverse events (TRAEs) were undertaken.
RESULTS
The analysis included six studies with a total of 858 patients. Compared with the three other second-line regimens, FOLFIRINOX had a significantly longer PFS (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.52, 0.89) and OS (HR 0.71, 95% CI 0.59, 0.86); and a significantly better ORR (HR 0.43, 95% CI 0.23, 0.80) and DCR (HR 0.71, 95% CI 0.58, 0.88). However, grade 3/4 adverse events were more frequently reported in patients administered FOLFIRINOX compared with the other three regimens.
CONCLUSION
FOLFIRINOX is recommended as a second-line chemotherapy regimen for patients with pancreatic cancer that have failed on gemcitabine-based first-line therapy.Research Registry number: reviewregistry1300.
Topics: Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Fluorouracil; Humans; Irinotecan; Leucovorin; Oxaliplatin; Pancreatic Neoplasms; Gemcitabine
PubMed: 35481414
DOI: 10.1177/03000605221093225 -
Medicine Dec 2021Recent randomized controlled trials revealed the combination of gemcitabine and capecitabine (GemCap) regime shows promising efficacy in pancreatic cancer patients.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recent randomized controlled trials revealed the combination of gemcitabine and capecitabine (GemCap) regime shows promising efficacy in pancreatic cancer patients. Here, we conducted a meta-analysis to compare the efficacy and safety of gemcitabine (Gem) with GemCap for pancreatic cancer.
METHODS
The database of MEDLINE (PubMed), EMBASE, Cochrane Central Controster of Controlled Trials, Web of Science was searched for relevant randomized controlled trials before 8 April, 2020. The outcomes were overall survival (OS), 12-month survival rate, progress free survival (PFS), partial response rate (PRR), objective response rate (ORR), and Grade 3/4 toxicities.
RESULTS
Five randomized controlled trials involving 1879 patients were included in this study. The results showed that GemCap significantly improves the OS (hazard ratio = 1.15, 95% CI: 1.037-1.276, P = .008), PFS (hazard ratio = 1.211, 95% CI 1.09-1.344, P = 0), PRR (relative risk (RR) = 0.649, 95% CI 0.488-0.862, P = .003), ORR (RR = 0.605, 95% CI 0.458-0.799, P = 0), and the overall toxicity (RR = 0.708, 95% CI 0.620-0.808, P = .000) compared to Gem alone. However, no significant difference was found in 12-month survival.
CONCLUSIONS
Despite a higher incidence of Grade 3/4 toxicity, GemCap was associated with better outcomes of OS, PFS, PRR, ORR, as compared with Gem, which is likely to become a promising therapy for pancreatic cancer.
Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Deoxycytidine; Drug Therapy, Combination; Humans; Pancreatic Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome; Gemcitabine
PubMed: 35049189
DOI: 10.1097/MD.0000000000027870 -
RMD Open Apr 2020To compare improvement in pain and physical function for patients treated with baricitinib, adalimumab, tocilizumab and tofacitinib monotherapy from randomised,... (Comparative Study)
Comparative Study
Comparative effectiveness of improvement in pain and physical function for baricitinib versus adalimumab, tocilizumab and tofacitinib monotherapies in rheumatoid arthritis patients who are naïve to treatment with biologic or conventional synthetic disease-modifying antirheumatic drugs: a...
OBJECTIVE
To compare improvement in pain and physical function for patients treated with baricitinib, adalimumab, tocilizumab and tofacitinib monotherapy from randomised, methotrexate (MTX)-controlled trials in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs)/biologic (bDMARD)-naïve RA patients using matching-adjusted indirect comparisons (MAICs).
METHODS
Data were from Phase III trials on patients receiving monotherapy baricitinib, tocilizumab, adalimumab, tofacitinib or MTX. Pain was assessed using a visual analogue scale (0-100 mm) and physical function using the Health Assessment Questionnaire-Disability Index (HAQ-DI). An MAIC based on treatment-arm matching, an MAIC with study-level matching and Bucher's method without matching compared change in outcomes between therapies. Matching variables included age, gender, baseline disease activity and baseline value of outcome measure.
RESULTS
With all methods, greater improvements were observed in pain and HAQ-DI at 6 months for baricitinib compared with adalimumab and tocilizumab (<0.05). Differences in treatment effects (TEs) favouring baricitinib for pain VAS for treatment-arm matching, study-level matching and Bucher's method, respectively, were -12, -12 and -12 for baricitinib versus adalimumab and -7, -7 and -9 for baricitinib versus tocilizumab; the difference in TEs for HAQ-DI was -0.28, -0.28 and -0.30 for adalimumab and -0.23, -0.23 and -0.26 for tocilizumab. For baricitinib versus tofacitinib, no statistically significant differences for pain improvement were observed except with one of the three methods (Bucher method) and none for HAQ-DI.
CONCLUSIONS
Results suggest greater pain reduction and improved physical function for baricitinib monotherapy compared with tocilizumab and adalimumab monotherapy. No statistically significant differences in pain reduction and improved physical function were observed between baricitinib and tofacitinib with the MAIC analyses.
Topics: Adalimumab; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Azetidines; Biological Products; Clinical Trials, Phase III as Topic; Disability Evaluation; Humans; Methotrexate; Network Meta-Analysis; Pain; Pain Measurement; Piperidines; Purines; Pyrazoles; Pyrimidines; Randomized Controlled Trials as Topic; Sulfonamides; Treatment Outcome
PubMed: 32371431
DOI: 10.1136/rmdopen-2019-001131 -
BioMed Research International 2019Direct-acting antivirals (DAAs) are modern treatments for chronic hepatitis C infection, but majority of available evidence on its treatment effect covers genotypes 1 to... (Meta-Analysis)
Meta-Analysis
Direct-acting antivirals (DAAs) are modern treatments for chronic hepatitis C infection, but majority of available evidence on its treatment effect covers genotypes 1 to 4. Therefore, the efficacy and safety of DAAs for genotypes 5 and 6 need to be analysed. Studies were identified from Medline, Scopus, and CENTRAL and a Chinese database CNKI, from inception until Dec 4, 2018. Clinical trials were included if they enrolled patients with genotypes 5 and/or 6 infection, any type of second-generation DAAs was studied, and sustained virological response was assessed at the 12 week after treatment (SVR12) as outcome measure. Meta-analysis using statistical program was applied for pooling proportions if data were sufficient (i.e., at least 2 studies). Thirteen studies were included in the analysis. Four studies assessed the efficacy of four DAA regimens in genotype 5 patients, which were mainly sofosbuvir (SOF) plus pegylated-interferon/ribavirin (PR) or other DAAs, with SVR12 ranging from 94.4% to 100%. Twelve studies assessed the efficacy of seven DAA regimens among genotype 6 patients, but only two DAA regimens (i.e., SOF + PR and SOF/ledipasvir) had sufficient data for pooling. The pooled SVR12 rates (95% CI) were 99.6% (92.2 to 100) for SOF + PR and 99.2% (96.5 to 100) for SOF/ledipasvir. No treatment-related serious adverse event was reported, while the nonserious adverse events were comparable to other genotypes. In conclusion, DAAs are effective and may be safe for the treatment of chronic hepatitis C genotypes 5 and 6. However, our evidence is based on noncomparative studies; hence, further larger-scale randomized controlled trials in these genotypes are still required.
Topics: Antiviral Agents; Benzimidazoles; Databases, Factual; Drug Therapy, Combination; Fluorenes; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Interferons; Ribavirin; Sofosbuvir; Uridine Monophosphate
PubMed: 31815126
DOI: 10.1155/2019/2301291 -
Cells May 20215-Aminoimidazole-4-carboxamide ribonucleoside (AICAr) has been one of the most commonly used pharmacological modulators of AMPK activity. The majority of early studies...
5-Aminoimidazole-4-carboxamide ribonucleoside (AICAr) has been one of the most commonly used pharmacological modulators of AMPK activity. The majority of early studies on the role of AMPK, both in the physiological regulation of metabolism and in cancer pathogenesis, were based solely on the use of AICAr as an AMPK-activator. Even with more complex models of AMPK downregulation and knockout being introduced, AICAr remained a regular starting point for many studies focusing on AMPK biology. However, there is an increasing number of studies showing that numerous AICAr effects, previously attributed to AMPK activation, are in fact AMPK-independent. This review aims to give an overview of the present knowledge on AMPK-dependent and AMPK-independent effects of AICAr on metabolism, hypoxia, exercise, nucleotide synthesis, and cancer, calling for caution in the interpretation of AICAr-based studies in the context of understanding AMPK signaling pathway.
Topics: AMP-Activated Protein Kinase Kinases; Aminoimidazole Carboxamide; Animals; Carcinogenesis; Cell Cycle; Energy Metabolism; Humans; Hypoglycemic Agents; Myocytes, Cardiac; Protein Kinases; Ribonucleotides
PubMed: 34064363
DOI: 10.3390/cells10051095 -
Clinical Therapeutics Nov 2019Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin lymphoma that can be either aggressive or indolent. Although MCL usually responds well to initial... (Comparative Study)
Comparative Study
PURPOSE
Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin lymphoma that can be either aggressive or indolent. Although MCL usually responds well to initial treatment with chemotherapy-based regimens, the disease often relapses or becomes refractory within a few years. Acalabrutinib is a highly selective, potent, covalent Bruton tyrosine kinase inhibitor with minimal off-target activity. WIthout head-to-head clinical trial data, estimation of the comparative efficacy and safety of new therapeutic entities provides valuable information for patients, clinicians, and health care payers. The objective of this analysis was to compare the efficacy and safety of acalabrutinib versus other targeted therapies employed for the treatment of relapsed/refractory MCL by using matching-adjusted indirect comparisons.
METHODS
Individual data from 124 patients treated with acalabrutinib in the Phase II ACE-LY-004 trial were adjusted to match average baseline characteristics of populations from studies using alternative targeted treatment regimens for relapsed/refractory MCL (for monotherapy: ibrutinib, bortezomib, lenalidomide, and temsirolimus; for combination therapies: ibrutinib + rituximab, bendamustine + rituximab, and lenalidomide + rituximab). Patient populations were matched on age, sex, race, Eastern Cooperative Oncology Group performance status, Simplified MCL International Prognostic Index score, tumor bulk, lactate dehydrogenase concentration, extranodal disease, bone marrow involvement, and number of previous treatment regimens. Outcomes assessed included overall response rate (ORR), complete response (CR) rate, overall survival (OS), progression-free survival (PFS), and adverse events.
FINDINGS
After matching, acalabrutinib was associated with significant increases in ORR and CR rate (estimated treatment difference [95% CI]) versus ibrutinib (ORR, 9.3% [0.3-18.3]; CR, 14.9% [5.4-24.3]), bortezomib (ORR, 50.6% [40.2-61.0]; CR, 18.8% [9.1-28.5]), lenalidomide (ORR, 38.1% [27.1-49.1]; CR, 43.5% [34.8-52.3]), and temsirolimus (ORR, 40.7% [31.0-50.4]; CR, 27.1% [19.2-35.0]). PFS (hazard ratio [95% CI]) with acalabrutinib was significantly increased versus bortezomib (0.36 [0.26-0.51]), lenalidomide (0.65 [0.48-0.89]), lenalidomide + rituximab (0.57 [0.35-0.93]), and temsirolimus (0.33 [0.24-0.45]). Acalabrutinib was associated with significantly increased OS (hazard ratio) versus bortezomib (0.36 [0.22-0.61]) and temsirolimus (0.32 [0.23-0.44]). The overall safety profile of acalabrutinib was similar or better compared with the monotherapies; however, infection risk increased versus bendamustine + rituximab, and anemia increased risk versus lenalidomide + rituximab and ibrutinib + rituximab.
IMPLICATIONS
This comparison of targeted therapies used in the treatment of relapsed/refractory MCL showed that acalabrutinib has the potential to provide increased response rates, with trends for increased PFS and OS, and an improved safety profile.
Topics: Adenine; Antineoplastic Agents; Benzamides; Bortezomib; Humans; Lenalidomide; Lymphoma, Mantle-Cell; Neoplasm Recurrence, Local; Piperidines; Pyrazines; Pyrazoles; Pyrimidines; Rituximab; Sirolimus; Treatment Outcome
PubMed: 31699438
DOI: 10.1016/j.clinthera.2019.09.012 -
Journal of Medical Virology May 2021This critical appraisal aims to clarify which systematic reviews on COVID-19 treatment are based on high-value evidence. Hereby, the most profitable medicines can be... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This critical appraisal aims to clarify which systematic reviews on COVID-19 treatment are based on high-value evidence. Hereby, the most profitable medicines can be suggested.
METHODS
The mesh terms of "COVID-19 drug treatment" (Supplementary Concept) and "COVID-19 drug treatment" were sequentially utilized as search strategies in Medline and Science direct on October 18, 2020. Searches were confined to systematic reviews/meta-analyses. The Cochrane database was searched on November 1, 2020 with "COVID." With adding up four articles from other resources, 84 systematic reviews were considered for initial screening. Finally, 22 articles fulfilled the criteria and were assessed using PRISMA guidelines.
RESULTS
Increasing number of clinical trials from the onset of the COVID-19 pandemic has revealed that hydroxychloroquine and chloroquine are not only profitable but also deleterious. Lopinavir/ritonavir failed to maintain their initial efficacy in improving clinical symptoms and mortality rate. Steroids and tocilizumab were suggested in patients with intensely severe symptoms. Steroids reduced mechanical ventilation and death in severely ill patients. Plasma or immunoglobulins effects are absolutely controversial. Favorable impressions of remdesivir have been relied on for the early onset of this drug. Hypotension and abnormal liver function tests were realized as its side effects. Favipiravir has resulted in a higher viral clearance than remdesivir. However, this claim needs to be proved with subsequent clinical trials.
CONCLUSIONS
Currently, remdesivir and favipiravir are advantageous drugs that should be administered in the early phases. Their side effects are not well known and need to be found in the following research projects. Steroids and tocilizumab have been considered beneficial in the cytokine storm phase.
Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; COVID-19; Chloroquine; Cytokine Release Syndrome; Databases, Factual; Humans; Hydroxychloroquine; Immunoglobulins; Lopinavir; Pandemics; Pyrazines; Respiration, Artificial; Ritonavir; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33463727
DOI: 10.1002/jmv.26811 -
BMC Cancer Jul 2020Pancreatic cancer has a poor prognosis and few choices of therapy. For patients with adequate performance status, FOLFIRINOX or gemcitabine plus nab-paclitaxel are... (Comparative Study)
Comparative Study Meta-Analysis
Meta-analysis examining overall survival in patients with pancreatic cancer treated with second-line 5-fluorouracil and oxaliplatin-based therapy after failing first-line gemcitabine-containing therapy: effect of performance status and comparison with other regimens.
BACKGROUND
Pancreatic cancer has a poor prognosis and few choices of therapy. For patients with adequate performance status, FOLFIRINOX or gemcitabine plus nab-paclitaxel are preferred first-line treatment. 5-Fluorouracil (5-FU)-based therapy (e.g. FOLFIRI, OFF, or FOLFOX) are often used in patients who previously received gemcitabine-based regimens. A systematic review was conducted of the safety and efficacy of FOLFOX for metastatic pancreatic cancer following prior gemcitabine-based therapy. A Bayesian fixed-effect meta-analysis with adjustment of patient performance status (PS) was conducted to evaluate overall survival (OS) and compare outcomes with nanoliposomal irinotecan combination therapy.
METHODS
PubMed.gov , FDA.gov , ClinicalTrials.gov , congress abstracts, Cochrane.org library, and EMBASE database searches were conducted to identify randomized controlled trials of advanced/metastatic disease, prior gemcitabine-based therapy, and second-line treatment with 5-FU and oxaliplatin. The database search dates were January 1, 1990-June 30, 2019. Endpoints were OS and severe treatment-related adverse events (TRAEs). Trial-level PS scores were standardized by converting Karnofsky grade scores to Eastern Cooperative Oncology Group (ECOG) Grade, and overall study-weighted PS was calculated based on weighted average of all patients.
RESULTS
Of 282 studies identified, 11 randomized controlled trials (N = 454) were included in the meta-analysis. Baseline weighted PS scores predicted OS in 10 of the 11 studies, and calculated PS scores of 1.0 were associated with a median OS of 6.3 months (95% posterior interval, 5.4-7.4). After adjusting for baseline PS, FOLFOX had a similar treatment effect profile (median OS, range 2.6-6.7 months) as 5-FU/leucovorin plus nanoliposomal irinotecan therapy (median OS, 6.1 months; 95% confidence interval 4.8-8.9). Neutropenia and fatigue were the most commonly reported Grade 3-4 TRAEs associated with FOLFOX.
CONCLUSIONS
Baseline PS is a strong prognostic factor when interpreting the efficacy of 5-FU and oxaliplatin-based therapy of pancreatic cancer after progression on first-line gemcitabine-based regimens. When baseline PS is considered, FOLFOX has a similar treatment effect as 5-FU and nanoliposomal irinotecan therapy and a comparable safety profile. These findings suggest that 5-FU and oxaliplatin-based therapies remain an acceptable and alternative second-line treatment option for patients with pancreatic cancer and adequate PS (e.g. ECOG 0-1) following gemcitabine treatment.
Topics: Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Resistance, Neoplasm; Drug-Related Side Effects and Adverse Reactions; Fluorouracil; Humans; Karnofsky Performance Status; Leucovorin; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms; Prognosis; Randomized Controlled Trials as Topic; Risk Factors; Survival Analysis; Treatment Outcome; Gemcitabine
PubMed: 32641104
DOI: 10.1186/s12885-020-07110-x -
An overview of the safety, clinical application and antiviral research of the COVID-19 therapeutics.Journal of Infection and Public Health Oct 2020Since a novel coronavirus pneumonia outbreak in late December 2019, coronavirus disease -19 (COVID-19) epidemic has gradually spread worldwide, becoming a major public...
Since a novel coronavirus pneumonia outbreak in late December 2019, coronavirus disease -19 (COVID-19) epidemic has gradually spread worldwide, becoming a major public health event. No specific antivirals are currently available for COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The treatments for COVID-19 are mainly based on the experiences of similar virus such SARS-CoV, MERS-CoV, HIV and influenza viruses. Scientists have taken great efforts to investigate the effective methods for the treatment of COVID-19. Up to now, there are over 1000 clinical studies for COVID-19 all over the world. In this article, we reviewed the current options for COVID-19 therapy including small molecules such as Remdesivir, Favipiravir, Lopinavir/Ritonavir etc, peptide inhibitors of ACE2, Traditional Chinese Medicines and Biologics such as SARS-CoV-2-specific neutralizing antibodies, mesenchymal stem cells and vaccines etc. Meanwhile, we systematically reviewed their clinical safety, clinical applications and progress of antiviral researches. The therapeutic effect of these antiviral drugs is summarized and compared, hoping to provide some ideas for clinical options of COVID-19 treatment and also provide experiences for the life-threatening virus diseases in the future.
Topics: Adenosine Monophosphate; Alanine; Amides; Angiotensin-Converting Enzyme Inhibitors; Antimalarials; Antiviral Agents; Betacoronavirus; Biomedical Research; COVID-19; Coronavirus Infections; Drug Combinations; Drug Development; Drugs, Chinese Herbal; Humans; Hydroxychloroquine; Immunization, Passive; Indoles; Interferons; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Ribavirin; Ritonavir; SARS-CoV-2; COVID-19 Serotherapy
PubMed: 32684351
DOI: 10.1016/j.jiph.2020.07.004 -
Scientific Reports Oct 2021Treatment outcomes between FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and GNP (gemcitabine with albumin-bound paclitaxel) as first-line... (Meta-Analysis)
Meta-Analysis
Treatment outcomes between FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and GNP (gemcitabine with albumin-bound paclitaxel) as first-line chemotherapy regimens for metastatic pancreatic cancer (PC) were assessed according to ethnic groups categorized as Western or Asian subgroups. PubMed, EMBASE, and Cochrane library were searched. Thirteen studies were eligible in this meta-analysis. Overall survival was not significantly different between FOLFIRINOX and GNP (HR 1.00, 95% CI 0.83-1.20, P = 0.990). However, the Western subgroup showed a higher survival benefit for FOLFIRINOX over GNP (HR 0.84, 95% CI 0.74-0.95, P = 0.006) whereas the Asian subgroup showed the survival benefit for GNP over FOLFIRINOX (HR 1.29, 95% CI 1.03-1.60, P = 0.030). Progression free survival was not significantly different between the two regimens in the Western subgroup (HR 1.01, 95% CI 0.84-1.20, P = 0.950) and the Asian subgroup (HR 1.13, 95% CI 0.97-1.33, P = 0.110). Occurrence of febrile neutropenia was significantly higher in FOLFIRINOX at both ethnic subgroups; however, that of peripheral neuropathy was significantly higher only in GNP of the Asian subgroup. Therefore, pharmacoethnicity might be a factor worth considering when deciding on a frontline chemotherapeutic regimen although the overall survival was not significantly different between FOLFIRINOX and GNP for metastatic PCs.
Topics: Albumins; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Ethnicity; Fluorouracil; Humans; Irinotecan; Leucovorin; Neoplasm Metastasis; Oxaliplatin; Paclitaxel; Pancreatic Neoplasms; Treatment Outcome; Gemcitabine
PubMed: 34635731
DOI: 10.1038/s41598-021-99647-5