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The Cochrane Database of Systematic... Jun 2015Despite modern antimicrobials and supportive therapy, bacterial and fungal infections are still major complications in people with prolonged disease-related or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite modern antimicrobials and supportive therapy, bacterial and fungal infections are still major complications in people with prolonged disease-related or therapy-related neutropenia. Since the late 1990s there has been increasing demand for donated granulocyte transfusions to treat or prevent severe infections in people who lack their own functional granulocytes. This is an update of a Cochrane review first published in 2009.
OBJECTIVES
To determine the effectiveness and safety of prophylactic granulocyte transfusions compared with a control population not receiving this intervention for preventing all-cause mortality, mortality due to infection, and evidence of infection due to infection or due to any other cause in people with neutropenia or disorders of neutrophil function.
SEARCH METHODS
We searched for randomised controlled trials (RCTs) and quasi-RCTs in the Cochrane Central Register of Controlled Trials (Cochrane Library 2015, Issue 3), MEDLINE (from 1946), EMBASE (from 1974), CINAHL (from 1937), theTransfusion Evidence Library (from 1980) and ongoing trial databases to April 20 2015.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs comparing people receiving granulocyte transfusions to prevent the development of infection with a control group receiving no granulocyte transfusions. Neonates are the subject of another Cochrane review and were excluded from this review. There was no restriction by outcomes examined, but this review focuses on mortality, mortality due to infection and adverse events.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
Twelve trials met the inclusion criteria. One trial is still ongoing, leaving a total of 11 trials eligible involving 653 participants. These trials were conducted between 1978 and 2006 and enrolled participants from fairly comparable patient populations. None of the studies included people with neutrophil dysfunction. Ten studies included only adults, and two studies included children and adults. Ten of these studies contained separate data for each arm and were able to be critically appraised. One study re-randomised people and therefore quantitative analysis was unable to be performed.Overall, the quality of the evidence was very low to low across different outcomes according to GRADE methodology. This was due to many of the studies being at high risk of bias, and many of the outcome estimates being imprecise.All-cause mortality was reported for nine studies (609 participants). There was no difference in all-cause mortality over 30 days between people receiving prophylactic granulocyte transfusions and those that did not (seven studies; 437 participants; RR 0.92, 95% CI 0.63 to 1.36, very low-quality evidence).Mortality due to infection was reported for seven studies (398 participants). There was no difference in mortality due to infection over 30 days between people receiving prophylactic granulocyte transfusions and those that did not (six studies; 286 participants; RR 0.69, 95% CI 0.33 to 1.44, very low-quality evidence).The number of people with localised or systemic bacterial or fungal infections was reported for nine studies (609 participants). There were differences between the granulocyte dose subgroups (test for subgroup differences P = 0.01). There was no difference in the number of people with infections over 30 days between people receiving prophylactic granulocyte transfusions and those that did not in the low-dose granulocyte group (< 1.0 x 10(10) granulocytes per day) (four studies, 204 participants; RR 0.84, 95% CI 0.58 to 1.20; very low-quality evidence). There was a decreased number of people with infections over 30 days in the people receiving prophylactic granulocyte transfusions in the intermediate-dose granulocyte group (1.0 x 10(10) to 4.0 x 10(10) granulocytes per day) (4 studies; 293 participants; RR 0.40, 95% CI 0.26 to 0.63, low-quality evidence).There was a decreased number of participants with bacteraemia and fungaemia in the participants receiving prophylactic granulocyte transfusions (nine studies; 609 participants; RR 0.45, 95% CI 0.30 to 0.65, low-quality evidence).There was no difference in the number of participants with localised bacterial or fungal infection in the participants receiving prophylactic granulocyte transfusions (six studies; 296 participants; RR 0.75, 95% CI 0.50 to 1.14; very low-quality evidence).Serious adverse events were only reported for participants receiving granulocyte transfusions and donors of granulocyte transfusions.
AUTHORS' CONCLUSIONS
In people who are neutropenic due to myelosuppressive chemotherapy or a haematopoietic stem cell transplant, there is low-grade evidence that prophylactic granulocyte transfusions decrease the risk of bacteraemia or fungaemia. There is low-grade evidence that the effect of prophylactic granulocyte transfusions may be dose-dependent, a dose of at least 10 x 10(10) per day being more effective at decreasing the risk of infection. There is insufficient evidence to determine any difference in mortality rates due to infection, all-cause mortality, or serious adverse events.
Topics: Adult; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Cause of Death; Child; Glucocorticoids; Granulocyte Colony-Stimulating Factor; Granulocytes; Humans; Leukocyte Disorders; Leukocyte Transfusion; Mycoses; Neutropenia; Randomized Controlled Trials as Topic
PubMed: 26118415
DOI: 10.1002/14651858.CD005341.pub3 -
PloS One 2016In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported.... (Review)
Review
BACKGROUND
In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance.
METHODOLOGY
We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context.
PRINCIPAL FINDINGS
Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations.
CONCLUSIONS
It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02017899, NCT02034500, NCT01771367, NCT01765413, NCT02523287.
Topics: Databases, Factual; Dysentery, Bacillary; Hematologic Tests; Humans; Neutropenia; Randomized Controlled Trials as Topic; Severity of Illness Index; Shigella Vaccines; Shigella sonnei; Vaccines
PubMed: 27490698
DOI: 10.1371/journal.pone.0157385 -
Cerebellum (London, England) Jun 2021Superficial siderosis describes haemosiderin deposition on the surface of the brain. When present on infratentorial structures, it can cause ataxia, sensorineural...
Superficial siderosis describes haemosiderin deposition on the surface of the brain. When present on infratentorial structures, it can cause ataxia, sensorineural hearing loss and pyramidal signs. There is no proven treatment and patients experience slow progression of symptoms. Iron-chelating agents have been suggested as a therapeutic option and deferiprone is suited as it crosses the blood-brain barrier. However, deferiprone is reported to have a 1-2% risk of agranulocytosis. We performed a systematic review on treatment of infratentorial superficial siderosis with deferiprone based on PRISMA guidelines. Studies were included if in English or an English language translation was available, were about human subjects and referred to patients with ataxia. Studies were excluded if they did not possess an English translation, included animal studies or did not have ataxia. Studies were excluded if they discussed cerebral amyloid angiopathy or siderosis of other regions. Eleven papers were included. We identified 69 patients. Seventeen patients (25%) discontinued the drug. The most encountered adverse effect was anaemia (21.7%). Neutropaenia was observed in 8.7% and agranulocytosis in 5.8% of patients. Clinically, response varied, and stability or improvement was seen across neurological domains in 6 studies while 5 showed a mixed response. On imaging, 13 (28.9%) patients improved, 24 (53.3%) stabilised and 8 (17.8%) deteriorated. A prospective international centralised register of patients should be developed to inform the design and conduct of a multicentre, placebo-controlled, randomised clinical trial to evaluate the efficacy of deferiprone. The evidence from this systematic review is that deferiprone is a promising intervention.
Topics: Animals; Deferiprone; Hemosiderin; Humans; Iron Chelating Agents; Randomized Controlled Trials as Topic; Siderosis
PubMed: 33409768
DOI: 10.1007/s12311-020-01222-7 -
Pediatric Blood & Cancer Oct 2019Routinely measurable biomarkers as predictors for adverse outcomes in febrile neutropenia could improve management through risk stratification. This systematic review... (Meta-Analysis)
Meta-Analysis
Updated systematic review and meta-analysis of the predictive value of serum biomarkers in the assessment and management of fever during neutropenia in children with cancer.
Routinely measurable biomarkers as predictors for adverse outcomes in febrile neutropenia could improve management through risk stratification. This systematic review assesses the predictive role of biomarkers in identifying events such as bacteraemia, clinically documented infections, microbiologically documented infection, severe sepsis requiring intensive care or high dependency care and death. This review collates 8319 episodes from 4843 patients. C-reactive protein (CRP), interleukin (IL)-6, IL-8 and procalcitonin (PCT) consistently predict bacteraemia and severe sepsis; other outcomes have highly heterogeneous results. Performance of the biomarkers at admission using different thresholds demonstrates that PCT > 0.5 ng/mL offers the best compromise between sensitivity and specificity: sensitivity 0.67 (confidence interval [CI] 0.53-0.79) specificity 0.73 (CI 0.66-0.77). Seventeen studies describe the use of serial biomarkers, with PCT having the greatest discriminatory role. Biomarkers, potentially with serial measurements, may predict adverse outcomes in paediatric febrile neutropenia and their role in risk stratification is promising.
Topics: Adolescent; Biomarkers; Child; Child, Preschool; Febrile Neutropenia; Female; Humans; Infant; Male; Neoplasms; Predictive Value of Tests; Young Adult
PubMed: 31250539
DOI: 10.1002/pbc.27887 -
The Australian and New Zealand Journal... Oct 2017Clozapine is the most effective medication for treatment-refractory schizophrenia; however, its use is contraindicated in people who have had previous clozapine-induced... (Review)
Review
Use of granulocyte-colony stimulating factor to prevent recurrent clozapine-induced neutropenia on drug rechallenge: A systematic review of the literature and clinical recommendations.
BACKGROUND
Clozapine is the most effective medication for treatment-refractory schizophrenia; however, its use is contraindicated in people who have had previous clozapine-induced neutropenia. Co-prescription of granulocyte-colony stimulating factor may prevent recurrent neutropenia and allow continuation or rechallenge of clozapine.
OBJECTIVE AND METHODS
Systematic review of literature reporting the use of granulocyte-colony stimulating factor to allow rechallenge or continuation of clozapine in people with previous episodes of clozapine-induced neutropenia. The efficacy of granulocyte-colony stimulating factor and predictors of successful rechallenge will be determined to elucidate whether evidence-based recommendations can be made regarding the use of granulocyte-colony stimulating factor in this context.
RESULTS
A total of 17 articles were identified that reported on clozapine rechallenge with granulocyte-colony stimulating factor support. In all, 76% of cases were able to continue clozapine at median follow-up of 12 months. There were no clear clinical or laboratory predictors of successful rechallenge; however, initial neutropenia was more severe in successful cases compared to unsuccessful cases. Cases co-prescribed lithium had lower success rates of rechallenge (60%) compared to those who were not prescribed lithium (81%). The most commonly reported rechallenge strategy was use of filgrastim 150-480 µg between daily to three times a week. There were no medication-specific side effects of granulocyte-colony stimulating factor reported apart from euphoria in one case. Three cases who failed granulocyte-colony stimulating factor had bacterial infection at time of recurrent neutropenia. No deaths were reported.
CONCLUSION
Preliminary data suggest granulocyte-colony stimulating factor is safe and effective in facilitating rechallenge with clozapine. Clinical recommendations for use are discussed.
Topics: Antipsychotic Agents; Clozapine; Granulocyte Colony-Stimulating Factor; Humans; Neutropenia; Schizophrenia
PubMed: 28747065
DOI: 10.1177/0004867417720516 -
Haematologica Apr 20246-mercaptopurine (6-MP) serves as the backbone in the maintenance regimens of acute lymphoblastic leukemia (ALL). We aimed to evaluate the influence of NUDT15 gene... (Meta-Analysis)
Meta-Analysis
Association of gene polymorphism with adverse reaction, treatment efficacy, and dose of 6-mercaptopurine in patients with acute lymphoblastic leukemia: a systematic review and meta-analysis.
6-mercaptopurine (6-MP) serves as the backbone in the maintenance regimens of acute lymphoblastic leukemia (ALL). We aimed to evaluate the influence of NUDT15 gene polymorphism on the risk of myelosupression, hepatotoxicity and interruption of 6-MP, as well as treatment efficacy and dose of 6-MP in ALL patients. A total of 24 studies with 3,374 patients were included in this meta-analysis. We found 9-fold higher risk of 6-MP induced leukopenia (odds ratio [OR] =9.00, 95% confidence interval [CI]: 3.73-21.74) and 2.5-fold higher risk of 6-MP-induced neutropenia (OR=2.52, 95% CI: 1.72-3.69) for NUDT15 c.415C>T variant carriers in the dominant model. Moreover, we found that the dose intensity of 6-MP in ALL patients with one NUDT15 c.415C>T variant alleles (CT) was 19% less than that in wild-type patients (CC) (mean differences: 19.43%, 95% CI: -25.36 to -13.51). The tolerable dose intensity of 6-MP in NUDT15 c.415C>T homozygote variant (TT) and heterozygote variant (CT) carriers was 49% and 15% less than that in wild-type patients, respectively. The NUDT15 c.415C>T variant group (CT+TT) had seven times (OR=6.98, 95% CI: 2.83-17.22) higher risk of developing 6-MP intolerance than the CC group. However, NUDT15 c.415C>T polymorphism did not appear significantly associated with hepatotoxicity, treatment interruption or relapse incidence. We concluded that NUDT15 c.415C>T was a good predictor for 6-MP-induced myelosuppression in ALL patients. The dose intensity of 6-MP in ALL patients with NUDT15 c.415C>T variants was significantly lower than that in wild-type patients. This research provided a basis for further investigation into relations between NUDT15 gene and adverse reaction, treatment efficacy and dose intensity of 6-MP.
Topics: Humans; Mercaptopurine; Pyrophosphatases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Polymorphism, Genetic; Neutropenia; Treatment Outcome; Chemical and Drug Induced Liver Injury
PubMed: 37794799
DOI: 10.3324/haematol.2023.282761 -
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 -
Brazilian Journal of Otorhinolaryngology 2021Tonsillectomy is the 2nd most common outpatient surgery performed on children in the United States of America. Its main complication is pain, which varies in intensity... (Review)
Review
INTRODUCTION
Tonsillectomy is the 2nd most common outpatient surgery performed on children in the United States of America. Its main complication is pain, which varies in intensity from moderate to severe. Dipyrone is one of the most widely used painkillers in the postoperative period in children. Its use, however, is controversial in the literature, to the point that it is banned in many countries due to its potential severe adverse effects. Because of this controversy, reviewing the analgesic use of dipyrone in the postoperative period of tonsillectomy in children is essential.
OBJECTIVE
The aim of this study was to review the analgesic use of dipyrone in the postoperative period of tonsillectomy in children.
METHODS
Systematic review of the literature, involving an evaluation of the quality of articles in the databases MEDLINE/Pubmed, EMBASE and Virtual Health Library, selected with a preestablished search strategy. Only studies with a randomised clinical trial design evaluating the use of dipyrone in the postoperative period of tonsillectomy in children were included.
RESULTS AND CONCLUSION
Only 2 randomised clinical trials were found. Both compared dipyrone, paracetamol, and placebo. We were unable to carry out a metanalysis because the studies were too heterogenous (dipyrone was used as pre-emptive analgesic in one and only postoperatively in another). The analgesic effect of dipyrone, measured by validated pain scales in childhood, was shown to be superior to placebo and similar to paracetamol. It appears that dipyrone exhibits a profile suitable for use in children. However, the scarcity of randomised clinical trials evaluating its analgesic effect in this age group leads to the conclusion that more well-designed studies are still needed to establish the role of dipyrone in the postoperative period of tonsillectomy in children.
Topics: Analgesia; Child; Dipyrone; Humans; Pain Measurement; Pain, Postoperative; Randomized Controlled Trials as Topic; Tonsillectomy
PubMed: 33485779
DOI: 10.1016/j.bjorl.2020.12.005 -
BMC Infectious Diseases May 2021Sepsis is a life-threatening and time-critical medical emergency; therefore, the early diagnosis of sepsis is essential to timely treatment and favorable outcomes for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sepsis is a life-threatening and time-critical medical emergency; therefore, the early diagnosis of sepsis is essential to timely treatment and favorable outcomes for patients susceptible to sepsis. Eosinopenia has been identified as a potential biomarker of sepsis in the past decade. However, its clinical application progress is slow and its recognition is low. Recent studies have again focused on the potential association between Eosinopenia and severe infections. This study analyzed the efficacy of Eosinopenia as a biomarker for diagnosis of sepsis and its correlation with pathophysiology of sepsis.
METHOD
The protocol for this meta-analysis is available in PROSPERO (CRD42020197664). We searched PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials CENTRAL databases to identify studies that met the inclusion criteria. Two authors performed data extraction independently. The pooled outcomes were calculated by TP (true positive), FP (false positive), FN (false negative), TN (true negative) by using bivariate meta-analysis model in STATA 14.0 software. Meanwhile, possible mechanisms of sepsis induced Eosinopenia was also analyzed.
RESULTS
Seven studies were included in the present study with a total number of 3842 subjects. The incidence of Eosinopenia based on the enrolled studies varied from 23.2 to 92.7%. For diagnosis of sepsis, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of Eosinopenia were 0.66 (95%CI [0.53-0.77]), 0.68 (95%CI [0.56-0.79]), 2.09 (95%CI [1.44-3.02]), 0.49 (95%CI [0.34-0.71]) and 4.23 (95%CI [2.15-8.31]), respectively. The area under the summary receiver operator characteristic curve (SROC) was 0.73 (95%CI [0.68-0.76]). Meta-regression analysis revealed that no single parameter accounted for the heterogeneity of pooled outcomes. For each subgroup of different eosinopenia cutoff values (50, 40, ≤25, 100), the sensitivity was 0.61, 0.79, 0.57, 0.54, and the specificity was 0.61, 0.75, 0.83, 0.51, respectively.
CONCLUSIONS
Our findings suggested that Eosinopenia has a high incidence in sepsis but has no superiority in comparison with conventional biomarkers for diagnosis of sepsis. However, eosinopenia can still be used in clinical diagnosis for sepsis as a simple, convenient, fast and inexpensive biomarker. Therefore, further large clinical trials are still needed to re-evaluate eosinopenia as a biomarker of sepsis.
Topics: Agranulocytosis; Biomarkers; Early Diagnosis; Eosinophils; Humans; Incidence; Odds Ratio; Sensitivity and Specificity; Sepsis
PubMed: 34030641
DOI: 10.1186/s12879-021-06150-3 -
The Cochrane Database of Systematic... Feb 2019Anthracyclines and taxanes are chemotherapeutic agents widely used in a sequential regimen in the adjuvant and neoadjuvant treatment of early breast cancer to reduce the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anthracyclines and taxanes are chemotherapeutic agents widely used in a sequential regimen in the adjuvant and neoadjuvant treatment of early breast cancer to reduce the risk of cancer recurrence. Standard practice is to administer anthracycline-based chemotherapy followed by a taxane. Anthracyclines tend to be administered first as they were established before taxanes for treatment of early breast cancer.
OBJECTIVES
To assess whether the sequence in which anthracyclines and taxanes are administered affects outcomes for people with early breast cancer receiving adjuvant or neoadjuvant therapy.
SEARCH METHODS
We searched Cochrane Breast Cancer's Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 1 February 2018.
SELECTION CRITERIA
Randomised controlled trials comparing administering a taxane prior to an anthracycline with taxane following anthracycline to people with early breast cancer receiving chemotherapy. The studies needed to have reported on at least one of our outcomes of interest, which included overall survival, disease-free survival, pathological response, treatment adherence, toxicity and quality of life.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data, assessed risk of bias and quality of the evidence. The primary outcome measure was overall survival. Secondary outcomes included disease-free survival, pathological response (in the neoadjuvant setting only), adverse events, treatment adherence and quality of life. For time-to-event outcomes of overall survival and disease-free survival, we derived hazard ratios (HRs) with 95% confidence intervals (CI) where possible. For dichotomous outcomes of pathological complete response, treatment adherence and adverse events, we reported the treatment effect as a risk ratio (RR) with 95% CI where possible. We used GRADE to assess the certainty of the evidence separately for the neoadjuvant and adjuvant settings.
MAIN RESULTS
There were 1415 participants in five neoadjuvant studies and 280 participants in four adjuvant studies involving five treatment comparisons. Four of the five neoadjuvant studies collected data for the primary outcome (overall survival) and two studies had data available; one of the four adjuvant studies collected overall survival data.The neoadjuvant studies suggested that the administration of taxanes first probably resulted in little to no difference in overall survival (HR 0.80, 95% CI 0.60 to 1.08; 947 participants; 2 studies; moderate-certainty evidence) and disease-free survival (HR 0.84, 95% CI 0.65 to 1.09; 828 participants; 1 study; moderate-certainty evidence). Administration of taxanes first also resulted in little to no difference in pathological complete response (absence of cancer in the breast and axilla: RR 1.15, 95% CI 0.96 to 1.38; 1280 participants; 4 studies; high-certainty evidence). However, there appeared to be a trend in favour of taxanes first. Studies reported treatment adherence using a range of measures. Administration of taxanes first probably did not increase the likelihood of requiring dose reductions compared to administration of anthracyclines first (RR 0.81, 95% CI 0.59 to 1.11; 280 participants; 1 study; moderate-certainty evidence). There was probably little to no difference in the risk of grade 3/4 neutropenia (RR 1.25, 95% CI 0.86 to 1.82; 280 participants, 1 study; moderate-certainty evidence) or grade 3/4 neurotoxicity (RR 0.95, 95% CI 0.55 to 1.65; 1108 participants; 2 studies; low-certainty evidence) when taxanes were given first. There were no data on quality of life.Only one adjuvant study collected data on overall survival and disease-free survival but did not report data. Administration of taxanes first reduced the risk of grade 3/4 neutropenia (RR 0.62, 95% CI 0.40 to 0.97; 279 participants; 4 studies, 5 treatment comparisons; high-certainty evidence) and appeared to result in little to no difference in grade 3/4 neurotoxicity (RR 0.78, 95% CI 0.25 to 2.46; 162 participants; 3 studies; low-certainty evidence). There was probably little to no difference in the proportions experiencing dose delays when taxanes are given first compared to anthracyclines given first (RR 0.76, 95% CI 0.52 to 1.12; 238 participants; 3 studies, 4 treatment comparisons; moderate-certainty evidence). One study reported on quality of life and indicated that scores (using the Functional Assessment of Cancer Therapy - Breast Cancer (FACT-B) validated questionnaire) were similar in both groups though did not provide numerical data.
AUTHORS' CONCLUSIONS
In the neoadjuvant setting, there is high- to low-certainty evidence of equivalent outcomes for the sequence in which taxanes are delivered. In the adjuvant setting, none of the studies reported on overall survival or disease-free survival. In most institutions, standard practice would be to deliver anthracycline followed by taxane, and currently available data do not support a change in this practice. We wait for the full-text publication of a relevant neoadjuvant study for women with HER2-negative breast cancer for inclusion in an update of this review.
Topics: Anthracyclines; Antibiotics, Antineoplastic; Antineoplastic Agents; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Disease-Free Survival; Docetaxel; Doxorubicin; Drug Administration Schedule; Epirubicin; Female; Fluorouracil; Humans; Neoadjuvant Therapy; Nervous System; Neutropenia; Paclitaxel; Quality of Life; Randomized Controlled Trials as Topic; Taxoids
PubMed: 30776132
DOI: 10.1002/14651858.CD012873.pub2