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Journal of Rehabilitation Medicine May 2019To investigate the efficacy and safety of drug interventions to promote motor recovery post-stroke.
OBJECTIVE
To investigate the efficacy and safety of drug interventions to promote motor recovery post-stroke.
DATA SOURCES
CENTRAL, CINAHL, Embase, MEDLINE, SCOPUS and Web of Science.
STUDY SELECTION
Published human randomized controlled trials in which the primary intervention was a drug administered to promote motor recovery post-stroke, vs placebo.
DATA EXTRACTION
Standardized pro forma used to extract safety and efficacy data; Cochrane Collaboration risk of bias assessment tool performed to assess risk of bias.
DATA SYNTHESIS
Fifty randomized controlled trials from 4,779 citations were included. An overall trend of high risk of attrition (n = 27) and reporting bias (n = 36) was observed. Twenty-eight different drug interventions were investigated, 18 of which demonstrated statistically significant results favouring increased motor recovery compared with control intervention. Forty-four studies measured safety; no major safety concerns were reported.
CONCLUSION
Candidate drug interventions promoting motor recovery post-stroke were identified, specifically selective serotonin reuptake inhibitors and levodopa; however, the high risk of bias in many trials is concerning. Drugs to improve motor function remain an important area of enquiry. Future research must focus on establishing the right drug intervention to be administered at an optimal dose and time, combined with the most effective adjuvant physical therapy to drive stroke recovery.
Topics: Humans; Physical Therapy Modalities; Randomized Controlled Trials as Topic; Stroke; Stroke Rehabilitation
PubMed: 30805655
DOI: 10.2340/16501977-2536 -
The Lancet. Oncology Mar 2019Although frequently used as a primary endpoint, disease-free survival has not been validated as a surrogate for overall survival in early breast cancer. We investigated... (Meta-Analysis)
Meta-Analysis
Disease-free survival as a surrogate for overall survival in patients with HER2-positive, early breast cancer in trials of adjuvant trastuzumab for up to 1 year: a systematic review and meta-analysis.
BACKGROUND
Although frequently used as a primary endpoint, disease-free survival has not been validated as a surrogate for overall survival in early breast cancer. We investigated this surrogacy in the adjuvant setting of treatment with anti-HER2 antibodies.
METHODS
In a systematic review and meta-analysis, we identified published and non-published randomised controlled trials with completed accrual and available disease-free survival and overall survival results for the intention-to-treat population as of September 2016. Bibliographic databases (MEDLINE, Embase, and Cochrane Central Register of Controlled Trials), clinical trial registries (Clinicaltrials.gov, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform, and PharmNet.Bund), and trial registries from relevant pharmaceutical companies were searched. Eligibility for treatment of HER2-positive early breast cancer required at least one group to have an anti-HER antibody treatment (ie, trastuzumab, pertuzumab, or trastuzumab emtansine) planned for 12 months, and at least one control arm with chemotherapy without the antibody, a lower total dose or duration of the antibody, or observation alone. Units of analysis were contrasts: two-group trials gave rise to one contrast, whereas trials with more than two groups gave rise to more than one contrast. We excluded trials enrolling patients with recurrent, metastatic, or non-invasive disease, and those testing neoadjuvant therapy exclusively. Our primary objective was to estimate patient-level and trial-level correlations between disease-free survival and overall survival. We measured the association between disease-free survival and overall survival using Spearman's correlation coefficient (r), and the association between hazard ratios (HRs) for disease-free survival and overall survival using R. We computed the surrogate threshold effect, the maximum HR for disease-free survival that statistically predicts an HR for overall survival less than 1·00 in a future trial.
FINDINGS
Eight trials (n=21 480 patients) gave rise to a full set (12 contrasts). Patient-level associations between disease-free and overall survival were strong (r=0·90 [95% CI 0·89-0·90]). Trial-level associations gave rise to values of R of 0·75 (95% CI 0·50-1·00) for the full set. Subgroups defined by nodal status and hormone receptor status yielded qualitatively similar results. Depending on the expected number of deaths in a future trial, the surrogate threshold effects ranged from 0·56 to 0·81, based on the full set.
INTERPRETATION
These findings suggest that it is appropriate to continue to use disease-free survival as a surrogate for overall survival in trials in HER-2-positive, early breast cancer. The key limitation of this study is the dependence of its results on the trials included and on the existence of an outlying trial.
FUNDING
Roche Pharma AG.
Topics: Ado-Trastuzumab Emtansine; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Administration Schedule; Female; Humans; Neoplasm Staging; Proportional Hazards Models; Receptor, ErbB-2; Treatment Outcome
PubMed: 30709633
DOI: 10.1016/S1470-2045(18)30750-2 -
JAMA Pediatrics Mar 2019Incidence of neonatal abstinence syndrome is rising rapidly, and optimal pharmacotherapy may meaningfully reduce length of treatment.
IMPORTANCE
Incidence of neonatal abstinence syndrome is rising rapidly, and optimal pharmacotherapy may meaningfully reduce length of treatment.
OBJECTIVE
To compare pharmacological therapies for neonatal abstinence syndrome.
DATA SOURCES
Systematic review and network meta-analysis of Medline (1946-June 2018), Embase (1974-June 2018), Cochrane CENTRAL (1966-June 2018), Web of Science (1900-June 2018), and ClinicalTrials.gov (June 2018).
STUDY SELECTION
Randomized clinical trials of pharmacological treatments for neonatal abstinence syndrome alone or in combination with adjuvant treatments. Abstract, title, and full-text screening were conducted independently by 2 reviewers (T.D. and C.G.).
DATA EXTRACTION AND SYNTHESIS
Data extraction was conducted independently by 2 reviewers (T.D. and C.G.) according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-Network Meta-Analyses guidelines. Quality was assessed with the Cochrane Risk of Bias tool and data were pooled with fixed-effect models as a result of the low number of trials that were included in the analysis.
MAIN OUTCOMES AND MEASURES
The primary outcome was the length of treatment. The length of stay, need for adjuvant therapy, and adverse events were considered as secondary outcomes.
RESULTS
Eighteen trials (N = 1072) were eligible for inclusion. The treatments that were included in the length of treatment analysis were buprenorphine, clonidine, diluted tincture of opium and clonidine, diluted tincture of opium, morphine, methadone, and phenobarbital. Sublingual buprenorphine was considered the optimal treatment for a reduction in the length of treatment (days: mean difference vs morphine, -12.75 [95% CI, -17.97 to -7.58]; median rank, 1 [3-1]) and length of stay (days: mean difference vs morphine, -11.43 [95% CI, -16.95 to -5.82]; median rank, 1 [3-1]) but not the need for adjuvant treatment (odds ratio vs morphine, 1.23 [95% CI, 0.46-3.44]; median rank, 3 [5-1]). The results were robust to bias but sensitive to imprecision.
CONCLUSIONS AND RELEVANCE
The current evidence suggests that buprenorphine is the optimal treatment for neonatal abstinence treatment, but limitations are considerable and wide-scale adoption requires a large multisite trial. Morphine, which is considered standard of care in most hospitals, was the lowest-ranked opioid for length of treatment and length of stay.
Topics: Analgesics, Opioid; Buprenorphine; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Network Meta-Analysis; Treatment Outcome
PubMed: 30667476
DOI: 10.1001/jamapediatrics.2018.5044 -
The Journal of Maternal-fetal &... Sep 2020To assess the additional benefits of 17-hydroxyprogesterone caproate (17-OHPC) therapy in preventing recurrent spontaneous preterm birth in women with an... (Meta-Analysis)
Meta-Analysis
To assess the additional benefits of 17-hydroxyprogesterone caproate (17-OHPC) therapy in preventing recurrent spontaneous preterm birth in women with an ultrasound-indicated cerclage. Electronic databases (Medline, Scopus, ClinicalTrials.gov, PROSPERO, Embase, Scielo, and the Cochrane Central Register of Controlled Trials) were searched for studies published before September 2018. Keywords included "preterm birth", "ultrasound-indicated cerclage", "pregnancy" and "17-hydroxyprogesterone caproate". Studies comparing ultrasound-indicated cerclage alone to cerclage plus 17-OHPC were included. The primary outcome measure was preterm birth at <35 weeks of gestation. Secondary outcome measures include preterm birth <24 weeks, <28 weeks, <32 weeks and <37 weeks of gestation, necrotizing enterocolitis (NEC), fetal birth weight, and intraventricular hemorrhage (grades III and IV). Meta-analysis was performed using the random effects model of DerSimonian and Laird. Risk of bias and quality assessment was performed using the risk of bias in nonrandomized studies of interventions (ROBINS-I). Four studies met inclusion criteria and were included in the final analysis. Of the 396 women who received ultrasound-indicated cerclage, 142 (35.9%) received adjuvant 17-OHPC. The primary outcome, preterm birth <35 weeks of gestation, was present in three studies and 332/396 singleton pregnancies. Though there was a trend towards a reduced risk of preterm birth, the summary estimate of effect was not statistically significant when comparing cerclage alone to cerclage plus 17-OHPC at <35 weeks (relative risk (RR) 0.95, 95% CI 0.77-1.17). Similarly, we found no differences in preterm birth at <24 weeks (RR 0.30, 95% CI 0.06-1.60), <28 weeks (RR 0.57, 95% CI 0.13-2.53), and <32 weeks (RR 0.99, 95% CI 0.44-2.27) when comparing cerclage alone to cerclage plus 17-OHPC. There were no differences in fetal birth weight, intraventricular hemorrhage and necrotizing enterocolitis comparing cerclage alone to cerclage plus 17-OHPC. Intramuscular 17-OHPC in combination with ultrasound-indicated cerclage in women with prior preterm birth had no additional effect in reducing spontaneous recurrent preterm birth or improving perinatal outcomes.
Topics: 17 alpha-Hydroxyprogesterone Caproate; 17-alpha-Hydroxyprogesterone; Adjuvants, Pharmaceutic; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Pregnancy; Premature Birth
PubMed: 30626240
DOI: 10.1080/14767058.2019.1568406 -
Systematic Reviews Nov 2018Originator trastuzumab (Herceptin®; H) is an antibody-targeted therapy to treat patients with human epidermal growth factor receptor 2-positive (HER2+) early breast... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Originator trastuzumab (Herceptin®; H) is an antibody-targeted therapy to treat patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (EBC). We investigated the overall survival (OS) advantage conferred by the addition of H to chemotherapy for HER2+ EBC patients and how the OS advantage changed over time.
METHODS
A systematic literature review (SLR) identified randomized controlled trials (RCTs) and non-randomized studies (NRSs) published from January 1, 1990 to January 19, 2017, comparing systemic therapies used in the neoadjuvant/adjuvant settings to treat HER2+ EBC patients. Bayesian cumulative network meta-analyses (cNMAs) of OS were conducted to assess the published literature over time. Heterogeneity was assessed through sensitivity and subgroup analyses.
RESULTS
The SLR identified 31 unique studies (28 RCTs, 3 NRSs) included in the OS analyses from 2008 to 2016. In the reference case cNMA (RCTs alone), initial evidence demonstrated an OS advantage for H/chemotherapy compared with chemotherapy alone in HER2+ EBC patients. As additional OS data were published, the precision around this survival benefit strengthened over time. Both H/anthracycline-containing chemotherapy and H/non-anthracycline-containing chemotherapy regimens provided similar OS advantages for HER2+ EBC patients.
CONCLUSION
This analysis represents the most comprehensive SLR/cNMA to date of published OS data in HER2+ EBC studies. These findings demonstrate why H/chemotherapy is now the established standard of care in HER2+ EBC. In the case of H, the benefits of early patient access far outweighed the risk of waiting for more precise information.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42017055763.
Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Humans; Network Meta-Analysis; Receptor, ErbB-2; Survival Rate; Trastuzumab
PubMed: 30428932
DOI: 10.1186/s13643-018-0854-y -
Medicina (Kaunas, Lithuania) Jul 2018Pancreatic cancer is one of the most fatal cancers. Cytotoxic chemotherapy remains the mainstream treatment for unresectable pancreatic cancer. This systematic review...
BACKGROUND AND AIM
Pancreatic cancer is one of the most fatal cancers. Cytotoxic chemotherapy remains the mainstream treatment for unresectable pancreatic cancer. This systematic review evaluated and compared the overall survival (OS) and progression-free survival (PFS) outcomes obtained from recent phase 2 and 3 clinical trials of pancreatic cancer chemotherapy.
MATERIALS AND METHODS
Thirty-two studies were included and compared based on chemotherapy agents or combinations used. Additionally, outcomes of first-line versus second-line chemotherapy in pancreatic cancer were compared.
RESULTS
In studies that investigated the treatments in adjuvant settings, the highest OS reported was for S-1 in patients, who received prior surgical resection (46.5 months). In neoadjuvant settings, the combination of gemcitabine, docetaxel, and capecitabine prior to the surgical resection had promising outcomes (OS of 32.5 months). In non-adjuvant settings, the highest OS reported was for the combination of temsirolimus plus bevacizumab (34.0 months). Amongst studies that investigated second-line treatment, the highest OS reported was for the combination of gemcitabine plus cisplatin (35.5 months), then temsirolimus plus bevacizumab (34.0 months).
CONCLUSIONS
There is a need to develop further strategies besides chemotherapy to improve the outcomes in pancreatic cancer treatment. Future studies should consider surgical interventions, combination chemotherapy, and individualized second-line treatment based on the prior chemotherapy.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Deoxycytidine; Disease-Free Survival; Docetaxel; Female; Humans; Male; Neoadjuvant Therapy; Pancreatic Neoplasms; Survival Analysis; Treatment Outcome; Gemcitabine
PubMed: 30344279
DOI: 10.3390/medicina54030048 -
PloS One 2018Evidence is growing that low-dose aspirin used as an adjuvant treatment of cancer is associated with an increased survival and a reduction in metastatic spread. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence is growing that low-dose aspirin used as an adjuvant treatment of cancer is associated with an increased survival and a reduction in metastatic spread. We therefore extended up to August 2017 an earlier systematic search and meta-analyses of published studies of low-dose aspirin taken by patients with a diagnosis of cancer.
METHODS
Searches were completed in Medline and Embase to August 2017 using a pre-defined search strategy to identify reports of relevant studies. References in all the selected papers were scanned. Two reviewers independently applied pre-determined eligibility criteria and extracted data on cause-specific cancer deaths, overall mortality and the occurrence of metastatic spread. Meta-analyses were then conducted for different cancers and heterogeneity and publication bias assessed. Sensitivity analyses and attempts to reduce heterogeneity were conducted.
RESULTS
Analyses of 29 studies reported since an earlier review up to April 2015 are presented in this report, and these are then pooled with the 42 studies in our earlier publication. Overall meta-analyses of the 71 studies are presented, based on a total of over 120 thousand patients taking aspirin. Ten of the studies also give evidence on the incidence of metastatic cancer spread. There are now twenty-nine observational studies describing colorectal cancer (CRC) and post-diagnostic aspirin. Pooling the estimates of reduction by aspirin which are reported as hazard ratios (HR), gives an overall HR for aspirin and CRC mortality 0.72 (95% CI 0.64-0.80). Fourteen observational studies have reported on aspirin and breast cancer mortality and pooling those that report the association with aspirin as a hazard ratio gives HR 0.69 (0.53-0.90). Sixteen studies report on aspirin and prostate cancer mortality and a pooled estimate yields an HR of 0.87 (95% CI 0.73-1.05). Data from 12 reports relating to other cancers are also listed. Ten studies give evidence of a reduction in metastatic spread; four give a pooled HR 0.31 (95% CI 0.18, 0.54) and five studies which reported odds ratio of metastatic spread give OR 0.79 (0.66 to 0.95).
CONCLUSION
Being almost entirely from observational studies, the evidence of benefit from aspirin is limited. There is heterogeneity between studies and the results are subject to important biases, only some of which can be identified. Nevertheless, the evidence would seem to merit wide discussion regarding whether or not it is adequate to justify the recommendation of low-dose therapeutic aspirin, and if it is, for which cancers?
Topics: Adjuvants, Pharmaceutic; Antineoplastic Agents; Aspirin; Decision Making; Evidence-Based Medicine; Humans; Neoplasms; Observational Studies as Topic; Treatment Outcome
PubMed: 30252883
DOI: 10.1371/journal.pone.0203957 -
Medical Journal of the Islamic Republic... 2017Trastuzumab in combination with chemotherapy has long been established as a standard treatment for HER2-positive patients in early stage breast cancer (BC). The present...
Trastuzumab in combination with chemotherapy has long been established as a standard treatment for HER2-positive patients in early stage breast cancer (BC). The present study aimed at assessing the effectiveness of trastuzumab adjuvant therapy in early stage BC in overall survival (OS) and disease-free survival (DFS). A systematic review and meta-analysis was performed to evaluate the effectiveness of trastuzumab adjuvant therapy. PubMed, Cochrane library, Scopus, Web of Science, and Embase databases were searched for relevant RCTs from the beginning to February 2017. Quality assessment of studies was conducted using the Cochrane Risk of Bias Tool. The desired outcomes were OS and DFS. A total of 1818 articles were identified first, however, only 11 studies were eligible to be included in this study. Our findings and meta-analysis results revealed that trastuzumab is effective in increasing OS (OS hazard ratio: -0.286 ± 0.049, 95%CI (-0.381, - 0.191)) and improving DFS (DFS hazard ratio: -0.419± 0.077, 95%CI (-0.569, -0.269)). The most serious but negligible side effect of trastuzumab is congestive heart failure. Adding trastuzumab as adjuvant therapy in early stages of BC in HER2 positive patients could increase OS and DFS of the patients effectively.
PubMed: 29951389
DOI: 10.14196/mjiri.31.88 -
The Cochrane Database of Systematic... May 2018Necrotizing soft tissue infections (NSTIs) are severe and rapidly spreading soft tissue infections of the subcutaneous tissue, fascia, or muscle, which are mostly caused... (Review)
Review
BACKGROUND
Necrotizing soft tissue infections (NSTIs) are severe and rapidly spreading soft tissue infections of the subcutaneous tissue, fascia, or muscle, which are mostly caused by bacteria. Associated rates of mortality and morbidity are high, with the former estimated at around 23%, and disability, sequelae, and limb loss occurring in 15% of patients. Standard management includes intravenous empiric antimicrobial therapy, early surgical debridement of necrotic tissues, intensive care support, and adjuvant therapies such as intravenous immunoglobulin (IVIG).
OBJECTIVES
To assess the effects of medical and surgical treatments for necrotizing soft tissue infections (NSTIs) in adults in hospital settings.
SEARCH METHODS
We searched the following databases up to April 2018: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers, pharmaceutical company trial results databases, and the US Food and Drug Administration and the European Medicines Agency websites. We checked the reference lists of included studies and reviews for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
RCTs conducted in hospital settings, that evaluated any medical or surgical treatment for adults with NSTI were eligible for inclusion. Eligible medical treatments included 1) comparisons between different antimicrobials or with placebo; 2) adjuvant therapies such as intravenous immunoglobulin (IGIV) therapy compared with placebo; no treatment; or other adjuvant therapies. Eligible surgical treatments included surgical debridement compared with amputation, immediate versus delayed intervention, or comparisons of number of interventions.RCTs of hyperbaric oxygen (HBO) therapy for NSTI were ineligible because HBO is the focus of another Cochrane Review.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary outcome measures were 1) mortality within 30 days, and 2) proportion of participants who experience a serious adverse event. Secondary outcomes were 1) survival time, and 2) assessment of long-term morbidity. We used GRADE to assess the quality of the evidence for each outcome.
MAIN RESULTS
We included three trials randomising 197 participants (62% men) who had a mean age of 55 years. One trial compared two antibiotic treatments, and two trials compared adjuvant therapies with placebo. In all trials, participants concomitantly received standard interventions, such as intravenous empiric antimicrobial therapy, surgical debridement of necrotic tissues, intensive care support, and adjuvant therapies. All trials were at risk of attrition bias and one trial was not blinded.Moxifloxacin versus amoxicillin-clavulanate One trial included 54 participants who had a NSTI; it compared a third-generation quinolone, moxifloxacin, at a dose of 400 mg given once daily, against a penicillin, amoxicillin-clavulanate, at a dose of 3 g given three times daily for at least three days, followed by 1.5 g three times daily. Duration of treatment varied from 7 to 21 days. We are uncertain of the effects of these treatments on mortality within 30 days (risk ratio (RR) 3.00, 95% confidence interval (CI) 0.39 to 23.07) and serious adverse events at 28 days (RR 0.63, 95% CI 0.30 to 1.31) because the quality of the evidence is very low.AB103 versus placebo One trial of 43 randomised participants compared two doses, 0.5 mg/kg and 0.25 mg/kg, of an adjuvant drug, a CD28 antagonist receptor (AB103), with placebo. Treatment was given via infusion pump for 10 minutes before, after, or during surgery within six hours after the diagnosis of NSTI. We are uncertain of the effects of AB103 on mortality rate within 30 days (RR of 0.34, 95% CI 0.05 to 2.16) and serious adverse events measured at 28 days (RR 1.49, 95% CI 0.52 to 4.27) because the quality of the evidence is very low.Intravenous immunoglobulin (IVIG) versus placebo One trial of 100 randomised participants assessed IVIG as an adjuvant drug, given at a dose of 25 g/day, compared with placebo, given for three consecutive days. There may be no clear difference between IVIG and placebo in terms of mortality within 30 days (RR 1.17, 95% CI 0.42 to 3.23) (low-certainty evidence), nor serious adverse events experienced in the intensive care unit (ICU) (RR 0.73 CI 95% 0.32 to 1.65) (low-certainty evidence).Serious adverse events were only described in one RCT (the IVIG versus placebo trial) and included acute kidney injury, allergic reactions, aseptic meningitis syndrome, haemolytic anaemia, thrombi, and transmissible agents.Only one trial reported assessment of long-term morbidity, but the outcome was not defined in the way we prespecified in our protocol. The trial used the Short Form Health Survey (SF36). Data on survival time were provided upon request for the trials comparing amoxicillin-clavulanate versus moxifloxacin and IVIG versus placebo. However, even with data provided, it was not possible to perform survival analysis.
AUTHORS' CONCLUSIONS
We found very little evidence on the effects of medical and surgical treatments for NSTI. We cannot draw conclusions regarding the relative effects of any of the interventions on 30-day mortality or serious adverse events due to the very low quality of the evidence.The quality of the evidence is limited by the very small number of trials, the small sample sizes, and the risks of bias in the included trials. It is important for future trials to clearly define their inclusion criteria, which will help with the applicability of future trial results to a real-life population.Management of NSTI participants (critically-ill participants) is complex, involving multiple interventions; thus, observational studies and prospective registries might be a better foundation for future research, which should assess empiric antimicrobial therapy, as well as surgical debridement, along with the placebo-controlled comparison of adjuvant therapy. Key outcomes to assess include mortality (in the acute phase of the condition) and long-term functional outcomes, e.g. quality of life (in the chronic phase).
Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; CD28 Antigens; Critical Care; Debridement; Female; Fluoroquinolones; Humans; Immunoglobulins, Intravenous; Male; Middle Aged; Moxifloxacin; Randomized Controlled Trials as Topic; Soft Tissue Infections
PubMed: 29851032
DOI: 10.1002/14651858.CD011680.pub2 -
PharmacoEconomics - Open Dec 2018Anti-estrogen (ER) endocrine therapy is an effective treatment strategy in reducing breast cancer mortality. This therapy has a better therapeutic index than... (Review)
Review
BACKGROUND
Anti-estrogen (ER) endocrine therapy is an effective treatment strategy in reducing breast cancer mortality. This therapy has a better therapeutic index than chemotherapy but can still affect patients' quality of life (QOL) over time.
OBJECTIVE
The objectives of this systematic review were to (1) describe QOL instruments used in ER-positive (ER+) non-metastatic breast cancer trials and (2) document the longitudinal effects of adjuvant endocrine therapy on the QOL of post-menopausal women with ER+ non-metastatic breast cancer.
METHODS
We searched three electronic bibliographic databases for articles published from inception to October 2017 that described (1) a randomized controlled trial (RCT) of non-metastatic breast cancer containing an adjuvant endocrine regimen in at least one arm; (2) the use of a patient self-report measure assessing general or breast cancer-specific QOL; and (3) QOL outcomes at multiple time points during follow-up of at least 5 years. All included trials were independently evaluated by two reviewers, and data were extracted using standardized forms.
RESULTS
In total, 13 studies met our inclusion criteria and were assessed in this review. The quality of the trials was reasonably good. The top three most commonly used QOL instruments in the trials were the Functional Assessment of Cancer Therapy/Functional Assessment of Chronic Illness Therapy, the Short Form-36 and the Menopause-Specific Quality of Life. Most studies found no differences between tamoxifen and aromatase inhibitor groups in terms of global QOL. QOL data affected treatment regimen recommendations in a few cases. A meta-analysis was not feasible because the RCTs included in our review varied in terms of sample size, comparators, QOL instrument used, and timing of QOL measurement. Additionally, as no search strategy has perfect sensitivity, specificity and accuracy, there is always a chance that potentially relevant articles were missed.
CONCLUSION
This systematic review suggests that the QOL of post-menopausal women is unlikely to be adversely affected by long-term use of adjuvant endocrine therapy. Efforts are needed to improve the quality of QOL reporting in clinical trials.
PubMed: 29470807
DOI: 10.1007/s41669-018-0070-7