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Frontiers in Immunology 2020There has been less volume of literature focusing on the Immune-related Hematological Adverse Drug Events (Hem-irAEs) of Immune Checkpoint Inhibitors (ICPis) in cancer...
There has been less volume of literature focusing on the Immune-related Hematological Adverse Drug Events (Hem-irAEs) of Immune Checkpoint Inhibitors (ICPis) in cancer patients. Furthermore, there has been no consensus about the management of hematological toxicity from immunotherapy in the recently published practice guidelines by the European Society for Medical Oncology (ESMO). We conducted a systematic review of case reports/series to describe the diagnosis and management of potentially rare and unrecognized Hem-irAEs. We searched Medline, OVID, Web of Science for eligible articles. Data were extracted on patient characteristics, Hem-irAEs, and management strategies. We performed quality assessment using the Pierson-5 evaluation scheme and causality assessment using the Naranjo scale. Our search retrieved 49 articles that described 118 cases. The majority of patients had melanoma (57.6%) and lung cancer (26.3%). The most common Hem-irAEs reported with ICPis (such as nivolumab, ipilimumab, and pembrolizumab) were thrombocytopenia, hemolytic and aplastic anemias. Less reported adverse events included agranulocytosis and neutropenia. Steroids were commonly used to treat these adverse events with frequent success. Other used strategies included intravenous immunoglobulins (IVIG), rituximab, and transfusion of blood components. The findings of this review provide more insights into the diagnosis and management of the rarely reported Hem-irAEs of ICPis.
Topics: Antineoplastic Agents, Immunological; Hematologic Diseases; Humans; Immune Checkpoint Inhibitors; Neoplasms
PubMed: 33193289
DOI: 10.3389/fimmu.2020.01354 -
Medicine Oct 2020Febrile neutropenia (FN) in cancer patients can be life threatening and require the timely antimicrobial agents treatment. (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Febrile neutropenia (FN) in cancer patients can be life threatening and require the timely antimicrobial agents treatment.
METHODS
To compare the effectiveness and safety of carbapenems versus β-lactams for FN. PubMed, Medline (Ovid SP), Cochrane CENTRAL, and Embase were searched up to March 2019. FN in patients due to undergoing chemotherapy and treated with carbapenems and β-lactams were included. Odds ratio (OR) and 95% confidence interval (CI) were estimated.
RESULTS
Fifty randomized controlled trials (RCTs) studies involving 10,995 participants were included. Carbapenems were more likely to experience treatment success without modification (OR = 1.34, 95% CI = 1.24-1.46) compared with β-lactams. Meropenem (OR = 1.36, 95% CI = 1.18-1.56; OR = 1.24, 95% CI = 1.01-1.53), imipenem/cilastatin (OR = 1.40, 95% CI = 1.19-1.65; OR = 1.31, 95% CI = 1.04-1.67) showed higher effectiveness from that by β-lactams monotherapy or in combination with aminoglycoside, respectively. Carbapenems-aminoglycoside combination therapy does not provide an advantage over carbapenems alone. Meropenem showed similar risk of adverse events (AEs) versus β-lactams. Imipenem/cilastatin was related to higher risk of AEs compared with β-lactams. There was no significant difference between carbapenems and β-lactams monotherapy or in combination.
CONCLUSION
Meropenem and imipenem/cilastatin monotherapy appears to be available treatment for FN compared with β-lactams. Imipenem/cilastatin was related to higher risk of AEs. Balancing the evidence for drug efficacy and side effects, meropenem monotherapy appears to be available treatment for FN. Individual centers should select the best matching therapy regimens according to local epidemiology and susceptibility patterns.
Topics: Anti-Bacterial Agents; Carbapenems; Drug Therapy, Combination; Febrile Neutropenia; Humans; Randomized Controlled Trials as Topic; beta-Lactams
PubMed: 33120768
DOI: 10.1097/MD.0000000000022725 -
Bioscience Reports Oct 2020Colorectal cancer (CRC) is a leading cause of cancer-related deaths across the world. Irinotecan (IRI) is commonly used to treat CRC, and IRI-based chemotherapy is... (Meta-Analysis)
Meta-Analysis
Colorectal cancer (CRC) is a leading cause of cancer-related deaths across the world. Irinotecan (IRI) is commonly used to treat CRC, and IRI-based chemotherapy is linked with adverse reaction and the efficacy of the treatment regimen. The gene UGT1A1 plays a central role in the IRI metabolic pathway. A polymorphism UGT1A1*6 has been widely researched which may be related to response of IRI-based chemotherapy in CRC. All relevant studies were strictly searched from PubMed, Embase, Cochrane Library and Web of Science databases to explore the associations between UGT1A1*6 and response of IRI-based chemotherapy with CRC. Nine articles comprising 1652 patients were included in the final combination. Meta-analysis showed G allele or GG had a lower risk of severe late-onset diarrhea compared with A/AA in allele model and homozygote model (G vs. A: OR = 0.53, 95% CI: 0.28-0.99, P=0.05; GG vs. AA: OR = 0.48, 95% CI: 0.23-0.99, P=0.05), no significant association was observed in other models. In addition, a significant association between UGT1A1*6 and neutropenia was observed in all models (G vs. A: OR = 0.57, 95% CI: 0.46-0.71, P=0.00; GG vs. AA: OR = 0.28, 95% CI: 0.17-0.45, P=0.01; GA vs. AA: OR = 0.42, 95% CI: 0.26-0.70, P=0.00; GG+GA vs. AA: OR = 0.32, 95% CI: 0.20-0.52, P=0.00; GG vs. AA+GA: OR = 0.40, 95% CI: 0.22-0.71, P=0.00), whereas, no relationship was found between UGT1A1*6 and clinical response among the different genotypes. UGT1A1*6 may be considered as a biomarker for IRI-based chemotherapy in CRC.
Topics: Colorectal Neoplasms; Diarrhea; Genetic Predisposition to Disease; Glucuronosyltransferase; Humans; Irinotecan; Neutropenia; Pharmacogenetics; Pharmacogenomic Variants; Polymorphism, Genetic; Risk Assessment; Risk Factors; Topoisomerase I Inhibitors; Treatment Outcome
PubMed: 32936306
DOI: 10.1042/BSR20200576 -
Supportive Care in Cancer : Official... Nov 2020PEGylated granulocyte colony-stimulating factor (G-CSF) is a safe alternative to G-CSF to improve chemotherapy-induced neutropenia (CIN). This superiority has resulted... (Meta-Analysis)
Meta-Analysis
BACKGROUND
PEGylated granulocyte colony-stimulating factor (G-CSF) is a safe alternative to G-CSF to improve chemotherapy-induced neutropenia (CIN). This superiority has resulted in its increased use by physicians; however, the superiority of PEGylated G-CSF for CIN in breast cancer has not been conclusively determined.
OBJECTIVES
To assess the superiority of PEGylated G-CSF for CIN in breast cancer in terms of effectiveness and safety via a systematic review and meta-analysis.
METHODS
A literature search in PubMed, Embase, Cochrane Library, and Web of Science was performed for eligible studies published from database inception to December 2019. All studies comparing PEGylated G-CSF and G-CSF for CIN of breast cancer were reviewed. After literature selection, data extraction and quality assessment were performed by two reviewers independently. Meta-analysis was conducted using Revman, version 5.2.
RESULTS
Nine randomized controlled trials were finally identified. The publication bias of these studies was acceptable. For the endpoint of effectiveness, analysis of the incidence/duration of grade ≥ 3 neutropenia, the duration of grade 4 neutropenia, the incidence of febrile neutropenia (FN), and the time to absolute neutrophil count recovery showed no advantage of PEGylated G-CSF over G-CSF for CIN of breast cancer (P > 0.05), with the premise of a sufficient dose of G-CSF according to the guidelines. No significant differences in grade 4 adverse events were observed between the groups (P = 0.29), and PEGylated G-CSF did not increase the incidence of skeletal and/or muscle pain compared with G-CSF (P = 0.32).
CONCLUSION
PEGylated G-CSF was as effective and safe as G-CSF to reduce CIN in breast cancer but did not show an obvious superiority. However, in clinical practice, PEGylated G-CSF has an obvious advantage in terms of convenience, which could improve patient's quality of life.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy-Induced Febrile Neutropenia; Female; Granulocyte Colony-Stimulating Factor; Humans; Neutropenia; Polyethylene Glycols; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins
PubMed: 32621264
DOI: 10.1007/s00520-020-05603-w -
Psychiatrike = Psychiatriki 2020Clozapine is an atypical antipsychotic used for the treatment of resistant schizophrenia, exhibiting significant advantages over other antipsychotic agents. Clozapine...
Clozapine is an atypical antipsychotic used for the treatment of resistant schizophrenia, exhibiting significant advantages over other antipsychotic agents. Clozapine efficacy is well established in people diagnosed with schizophrenia via reducing both positive and negative symptoms. Also, is associated with a low risk of extrapyramidal side effects compared to other antipsychotics. Despite the above, clozapine is an unpopular therapeutic option for patients not previously responded to other antipsychotics, because of adverse side effects, such as hyper-salivation and weight gain or critical side effects, i.e., risk for developing neutropenia and agranulocytosis and the need for a systematic and vigilant patients' monitoring, causing discomfort to them and increased expenses to the healthcare system. The aim of the present article is to describe (a) the development of a "clozapine treatment monitoring protocol", and (b) the monitoring process applied at the Department of Psychiatry of Aghioi Anargyroi Cancer Hospital in patients under clozapine treatment. For the protocol development a systematic review of the existing literature was conducted. An advanced search in Medline, CINAHL, Scopus and Google Scholar was conducted, as well as at the National Organization of Greece for Medicines database, with the following key- words: "clozapine", "clozapine protocol", "clozapine monitoring", "clozapine guidelines". Based on this procedure, the Victorian Consensus View protocol applied in Australia was evaluated as the most appropriate since it encompasses: (a) monitoring of multiple systems based on a holistic healthcare approach towards patients, and (b) Intense cardiovascular functioning monitoring, highly relevant to the Greek population due to increased incidence of myocarditis. Overall, the necessary interventions prior and after clozapine treatment initiation are, monitoring of heamatological and cardiovascular function and related side effects, metabolic monitoring and related side effects, monitoring of metabolic adverse effects, gastrointestinal and neurological adverse effects, hepatic function monitoring and related side effects. Clozapine treatment monitoring protocol applied at special settings, e.g., Clozapine Clinics, is highly beneficial, since the risk of neutropenia, agronulocytosis is minimized, while suicidal behavior and substance use are reduced along with risky health behaviors, i.e., nicotine use and sedentary lifestyle. The current protocol may be applied by mental healthcare professionals aiming to empower individuals with schizophrenia through promoting their independency and quality of life.
Topics: Clozapine; Greece; Humans; Schizophrenia; Schizophrenic Psychology
PubMed: 32544078
DOI: 10.22365/jpsych.2020.311.70 -
The Cochrane Database of Systematic... May 2020Glioblastoma is an uncommon but highly aggressive type of brain tumour. Significant gains have been achieved in the molecular understanding and the pathogenesis of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Glioblastoma is an uncommon but highly aggressive type of brain tumour. Significant gains have been achieved in the molecular understanding and the pathogenesis of glioblastomas, however clinical improvements are difficult to obtain for many reasons. The current standard of care involves maximal safe surgical resection followed by chemoradiation and then adjuvant chemotherapy European Organisation for Research and Treatment of Cancer and the NCIC Clinical Trials Group (EORTC-NCIC) protocol with a median survival of 14.6 months. Successive phase III international randomised controlled studies have failed to significantly demonstrate survival advantage with newer drugs. Epidermal growth factor receptor (EGFR) is observed to be aberrant in 30% to 60% of glioblastomas. The receptor aberrancy is driven by abnormal gene amplification, receptor mutation, or both, in particular the extracellular vIII domain. EGFR abnormalities are common in solid tumours, and the advent of anti-EGFR therapies in non-small cell lung cancer and colorectal adenocarcinomas have greatly improved clinical outcomes. Anti-EGFR therapies have been investigated amongst glioblastomas, however questions remain about its ongoing role in glioblastoma management. This review aimed to report on the available evidence to date and perform a systematic analysis on the risks and benefits of use of anti-EGFR therapies in glioblastomas.
OBJECTIVES
To evaluate the efficacy and harms of anti-EGFR therapies for glioblastoma in adults.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, EBM Reviews databases, with supplementary handsearches to identify all available and relevant studies to 20 April 2020.
SELECTION CRITERIA
All randomised controlled trials (RCTs) using anti-EGFR therapies in adults with glioblastoma were eligible for inclusion. Anti-EGFR therapies included tyrosine kinase inhibitors, monoclonal antibodies, or vaccines. The comparison included investigational product added to standard of care versus standard of care or placebo, or investigational product against standard of care or placebo.
DATA COLLECTION AND ANALYSIS
The authorship team screened the search results and recorded the extracted data for analysis. We used standard Cochrane methodology to performed quantitative meta-analysis if two or more studies had appropriate and available data. Otherwise, we conducted a qualitative and descriptive analysis. We used the GRADE system to rate the certainty of the evidence. The analysis was performed along the two clinical settings: first-line (after surgery) and recurrent disease (after failure of first line treatment). Where information was available, we documented overall survival, progression-free survival, adverse events, and quality of life data from eligible studies.
MAIN RESULTS
The combined searches initially identified 912 records (after removal of duplicates), and further screening resulted in 19 records for full consideration. We identified nine eligible studies for inclusion in the review. There were three first-line studies and six recurrent studies. Five studies used tyrosine kinase inhibitors (TKIs); two studies used monoclonal antibodies; and two studies used targeted vaccines. More recent studies presented greater detail in the conduct of their studies and thus had a lower risk of bias. We observed no evidence benefit in overall survival with the use of anti-EGFR therapy in the first-line or recurrent setting (hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.76 to 1.04; 3 RCTs, 1000 participants, moderate-certainty evidence; and HR 0.79, 95% CI 0.51 to 1.21, 4 RCTs, 489 participants, low-certainty evidence, respectively). All the interventions were generally well tolerated with low-certainty evidence for lymphopenia (odds ratio (OR) 0.97, 95% CI 0.19 to 4.81; 4 RCTs, 1146 participants), neutropenia (OR 1.29, 95% CI 0.82 to 2.03; 4 RCTs, 1146 participants), and thrombocytopenia (OR 3.69, 95% CI 0.51 to 26.51; 4 RCTs, 1146 participants). A notable toxicity relates to ABT-414, where significant ocular issues were detected. The addition of anti-EGFR therapy showed no evidence of an increase in progression-free survival (PFS) in the first-line setting (HR 0.94, 95% CI 0.81 to 1.10; 2 RCTs, 894 participants, low-certainty evidence). In the recurrent setting, there was an increase in PFS with the use of anti-EGFR therapy (HR 0.75, 95% CI 0.58 to 0.96, 3 RCTs, 275 participants, low-certainty evidence). The available quality of life assessment data showed that anti-EGFR therapies were neither detrimental or beneficial when compared to standard care (not estimable).
AUTHORS' CONCLUSIONS
In summary, there is no evidence of a demonstrable overall survival benefit with the addition of anti-EGFR therapy in first-line and recurrent glioblastomas. Newer drugs that are specially designed for glioblastoma targets may raise the possibility of success in this population, but data are lacking at present. Future studies should be more selective in pursuing people displaying specific EGFR targets.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Agents, Immunological; Brain Neoplasms; Cancer Vaccines; Disease Progression; ErbB Receptors; Glioblastoma; Humans; Lymphopenia; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Randomized Controlled Trials as Topic; Thrombocytopenia
PubMed: 32395825
DOI: 10.1002/14651858.CD013238.pub2 -
British Journal of Haematology Jun 2020Langerhans cell histiocytosis (LCH) is a rare protean disease that usually affects children. Few data are available for management of adult-onset cases. A complete...
Long-term efficacy and safety of 2CdA (cladribine) in extra-pulmonary adult-onset Langerhans cell histiocytosis: analysis of 23 cases from the French Histiocytosis Group and systematic literature review.
Langerhans cell histiocytosis (LCH) is a rare protean disease that usually affects children. Few data are available for management of adult-onset cases. A complete picture of the efficacy and safety of 2CdA (2-chlorodeoxyadenosine, cladribine) is lacking. We report a retrospective multicentre study of 23 adult LCH (a-LCH) patients who received single-agent 2CdA and a systematic literature review. All had previously received systemic therapy (vinblastine, n = 19). Response to 2CdA was evaluable in 22 cases. Overall response rate (ORR) was 91%. Complete response (CR) occurred in 11 cases (50%). Nine patients (39%) developed grade 3-4 neutropenia and/or severe infection. A literature review yielded 48 additional cases. A pooled analysis confirmed our findings (ORR: 88%, CR: 49%). CRs were rare with cumulative dose <50 mg/m . Disease progression rates were 20% and 30% at two and five years, respectively. Partial response (PR) to 2CdA was predictive of disease progression. Among eight re-treated patients, five went into CR, two in PR, and one died. Single-agent 2CdA is effective in reactivated a-LCH, including at intermediate doses. Toxicity, significant but acceptable, warrants infectious prophylaxis. Complete responders may enter prolonged remission. Further studies are needed to determine 2CdA sequencing with other agents (vinblastine, cytarabine).
Topics: Adult; Age of Onset; Aged, 80 and over; Antimetabolites; Cladribine; Dose-Response Relationship, Drug; Female; France; Histiocytosis, Langerhans-Cell; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Middle Aged; Neutropenia; Proportional Hazards Models; Remission Induction; Retrospective Studies; Sepsis; Virus Diseases
PubMed: 32191819
DOI: 10.1111/bjh.16449 -
Journal of Infection and Chemotherapy :... Jun 2020Empirical antifungal therapy is recommended in high-risk patients who have persistent febrile neutropenia (FN) despite broad-spectrum antibiotic therapy. Based on... (Meta-Analysis)
Meta-Analysis
Echinocandins versus non-echinocandins for empirical antifungal therapy in patients with hematological disease with febrile neutropenia: A systematic review and meta-analysis.
Empirical antifungal therapy is recommended in high-risk patients who have persistent febrile neutropenia (FN) despite broad-spectrum antibiotic therapy. Based on high-quality evidence, most guidelines recommend caspofungin. The aim of this study was to clarify whether echinocandins, including micafungin, are associated with improved clinical outcomes in patients with persistent FN. We conducted a meta-analysis of randomized controlled trials (RCTs) of empirical therapy with echinocandins and non-echinocandins for FN in patients with hematological disease. The primary outcome was all-cause mortality within 7 days after completion of therapy. Secondary outcomes included treatment success, and discontinuation of therapy because of adverse events. For subgroup analysis, we compared RCTs of echinocandins with liposomal amphotericin B. Six RCTs (four that evaluated caspofungin and two that evaluated micafungin) were included in the meta-analysis. Mortality and adverse events in echinocandin-treated patients were significantly lower than in those treated with non-echinocandins [risk ratio (RR) 0.70, 95% confidence interval (CI) 0.49-0.99; RR 0.48, 95% CI 0.33-0.71, respectively]. There was no significant difference in treatment success (RR 1.09, 95% CI 0.87-1.36). Mortality and adverse events in echinocandin-treated patients were significantly lower than in those treated with liposomal amphotericin B (RR 0.68, 95% CI 0.46-0.99; RR 0.53, 95% CI 0.37-0.74, respectively). In conclusion, patients with persistent FN treated with echinocandins had decreased risk of death and adverse events. Both caspofungin and micafungin may be recommended as first-line empirical antifungal therapy in these patients. However, the small number of enrolled patients and the lack of RCTs involving pediatric patients should be considered when using micafungin.
Topics: Amphotericin B; Antifungal Agents; Echinocandins; Febrile Neutropenia; Humans; Mycoses; Randomized Controlled Trials as Topic; Treatment Outcome; Voriconazole
PubMed: 32171659
DOI: 10.1016/j.jiac.2020.01.015 -
Medicine Feb 2020This meta-analysis assessed the clinical efficacy and safety of cefoperazone-sulbactam for empiric therapy febrile neutropenia. (Meta-Analysis)
Meta-Analysis
PURPOSE
This meta-analysis assessed the clinical efficacy and safety of cefoperazone-sulbactam for empiric therapy febrile neutropenia.
METHODS
The PubMed, Web of Science, EBSCO, Cochrane Library, Ovid Medline, EMBASE, and ClinicalTrial.gov database were searched through May 10, 2019. Only clinical trials comparing cefoperazone-sulbactam with other antibiotics for empiric treatment of febrile neutropenia were included. The primary outcome was treatment success without modification, and the secondary outcomes were all-cause mortality and adverse events (AEs).
RESULTS
Ten randomized controlled trials (RCTs) and 1 retrospective cohort study were included. Overall, cefoperazone-sulbactam exhibited a treatment success rate similar to those of comparator drugs for the treatment of febrile neutropenia (odds ratio [OR], 1.03; 95% confidence interval [CI], 0.85 to 1.24, I = 0%). A similar finding was noted in pooled analysis of 10 RCTs (OR, 1.07; 95% CI, 0.88 to 1.30, I = 0%). Subgroup analysis showed that cefoperazone-sulbactam had a treatment success rate similar to the rates of comparators for adults (OR, 1.10; 95% CI, 0.88 to 1.38, I = 0%) and children (OR, 0.96; 95% CI, 0.63 to 1.46, I = 0%). Cefoperazone-sulbactam did not differ significantly from comparators in the risks of all-cause mortality (OR, 0.96; 95% CI, 0.58 to 1.58, I = 0%) or common AEs, namely rash, nausea/vomiting, and superinfection.
CONCLUSION
The clinical efficacy and tolerability of cefoperazone-sulbactam are comparable to those of comparator drugs in the treatment of febrile neutropenia.
Topics: Anti-Bacterial Agents; Cefoperazone; Drug Therapy, Combination; Febrile Neutropenia; Humans; Sulbactam
PubMed: 32080150
DOI: 10.1097/MD.0000000000019321 -
Frontiers in Endocrinology 2019Granulocyte-colony-stimulating factor (G-CSF) is highly beneficial as a general treatment for anti-thyroid drug (ATD)-induced agranulocytosis. This meta-analysis aimed...
Granulocyte-colony-stimulating factor (G-CSF) is highly beneficial as a general treatment for anti-thyroid drug (ATD)-induced agranulocytosis. This meta-analysis aimed to assess the clinical effects of G-CSF and non-G-CSF on recovery duration in patients with ATD-induced agranulocytosis by analyzing the overall clinical outcomes. The PubMed, Embase, Ovid, Cochrane, Google Scholar, China National Knowledge Infrastructure (CNKI) databases were searched for published studies from 1900 to 2018. No language restriction was implemented. This meta-analysis included 10 published retrospective studies and one prospective study. Data were obtained from 11 trials (474 patients: 247 with G-CSF and 227 with non-G-CSF treatment). Compared with the non-G-CSF group, the G-CSF group presented shorter recovery duration [weighted mean difference (WMD) = -3.04 days, 95% confidence interval (95% CI): -4.38 to -1.69 ( = 4.43 = 0.000)]. However, the recovery duration varied across regions and recovery criteria. Asian patients achieved significant clinical outcomes [WMD = -3.16 days (95% CI: -4.58 to -1.74, = 0.000)] compared with European and South American patients [WMD = -2.19 days (95% CI: -7.38 to 3.01, = 0.409)]. Also, according to various recovery criteria, a duration of granulocyte count increase of more than 1.5 or 1.0 × 10/L [WMD = -3.50 days (95% CI: -4.82 to -2.18 = 0.000)] revealed a better treatment effect. G-CSF can significantly shorten the recovery duration in patients with ATD-induced agranulocytosis.
PubMed: 31824417
DOI: 10.3389/fendo.2019.00789