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Minerva Anestesiologica Apr 2023Midazolam hydrochloride is a widely accepted benzodiazepine for premedication in pediatric patients. However, there is no consistent conclusion regarding which route of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Midazolam hydrochloride is a widely accepted benzodiazepine for premedication in pediatric patients. However, there is no consistent conclusion regarding which route of administration is best. We performed a meta-analysis to assess the efficacy and safety of oral versus intranasal midazolam premedication in children.
EVIDENCE ACQUISITION
The PubMed, Embase, Cochrane Library, and Google Scholar databases were searched from inception to June 2022, for randomized controlled trials comparing oral versus intranasal midazolam. Primary outcomes included satisfactory mask acceptance for induction and satisfactory sedation at separation from parents. Secondary outcomes included the incidence of postoperative nausea and vomiting, incidence of nasal irritation, postoperative recovery time, and hemodynamic changes.
EVIDENCE SYNTHESIS
Data from 14 studies involving a total of 901 children were obtained. The results indicated that intranasal and oral midazolam premedication in children provided similar satisfactory mask acceptance for induction (RR, 1.02; 95% CI, 0.93-1.13; P=0.64; I=0%), satisfactory sedation at separation from parents (RR, 0.99; 95% CI, 0.89-1.10; P=0.90; I=57%), and postoperative recovery time (WMD, -8.01; 95% CI, -20.16-4.14; P=0.20; I=85%). Additionally, intranasal midazolam premedication was associated with lower incidence of postoperative nausea and vomiting (RR, 0.70; 95% CI, 0.51-0.96; P=0.03; I2=0%) and shorter onset time.
CONCLUSIONS
Differences between intranasal and oral midazolam in satisfactory mask acceptance for induction, satisfactory sedation at separation from parents, and postoperative recovery time were not significant. Intranasal midazolam premedication was associated with shorter onset time and higher incidence of nasal irritation.
Topics: Child; Humans; Midazolam; Hypnotics and Sedatives; Dexmedetomidine; Postoperative Nausea and Vomiting; Premedication; Administration, Intranasal
PubMed: 36852568
DOI: 10.23736/S0375-9393.22.16937-3 -
The Cochrane Database of Systematic... Sep 2017This review is the first update of a previously published review in The Cochrane Library (Issue 7, 2015). Interleukin-5 (IL-5) is the main cytokine involved in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review is the first update of a previously published review in The Cochrane Library (Issue 7, 2015). Interleukin-5 (IL-5) is the main cytokine involved in the activation of eosinophils, which cause airway inflammation and are a classic feature of asthma. Monoclonal antibodies targeting IL-5 or its receptor (IL-5R) have been developed, with recent studies suggesting that they reduce asthma exacerbations, improve health-related quality of life (HRQoL) and lung function. These are being incorporated into asthma guidelines.
OBJECTIVES
To compare the effects of therapies targeting IL-5 signalling (anti-IL-5 or anti-IL-5Rα) with placebo on exacerbations, health-related qualify of life (HRQoL) measures, and lung function in adults and children with chronic asthma, and specifically in those with eosinophilic asthma refractory to existing treatments.
SEARCH METHODS
We searched the Cochrane Airways Trials Register, clinical trials registries, manufacturers' websites, and reference lists of included studies. The most recent search was March 2017.
SELECTION CRITERIA
We included randomised controlled trials comparing mepolizumab, reslizumab and benralizumab versus placebo in adults and children with asthma.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and analysed outcomes using a random-effects model. We used standard methods expected by Cochrane.
MAIN RESULTS
Thirteen studies on 6000 participants met the inclusion criteria. Four used mepolizumab, four used reslizumab, and five used benralizumab. One study in benralizumab was terminated early due to sponsor decision and contributed no data. The studies were predominantly on people with severe eosinophilic asthma, which was similarly but variably defined. Eight included children over 12 years but these results were not reported separately. We deemed the risk of bias to be low, with all studies contributing data being of robust methodology. We considered the quality of the evidence for all comparisons to be high overall using the GRADE scheme, with the exception of intravenous mepolizumab because this is not currently a licensed delivery route.All of the anti-IL-5 treatments assessed reduced rates of 'clinically significant' asthma exacerbation (defined by treatment with systemic corticosteroids for three days or more) by approximately half in participants with severe eosinophilic asthma on standard of care (at least medium-dose inhaled corticosteroids (ICS)) with poorly controlled disease (either two or more exacerbations in the preceding year or Asthma Control Questionnaire (ACQ) 1.5 or more). Non-eosinophilic participants treated with benralizumab also showed a significant reduction in exacerbation rates, but no data were available for non-eosinophilic participants, and mepolizumab or reslizumab.We saw modest improvements in validated HRQoL scores with all anti-IL-5 agents in severe eosinophilic asthma. However these did not exceed the minimum clinically important difference for ACQ and Asthma Quality of Life Questionnaire (AQLQ), with St. George's Respiratory Questionnaire (SGRQ) only assessed in two studies. The improvement in HRQoL scores in non-eosinophilic participants treated with benralizumab, the only intervention for which data were available in this subset, was not statistically significant, but the test for subgroup difference was negative.All anti-IL-5 treatments produced a small but statistically significant improvement in mean pre-bronchodilator forced expiratory flow in one second (FEV) of between 0.08 L and 0.11 L.There were no excess serious adverse events with any anti-IL-5 treatment, and indeed a reduction in favour of mepolizumab that could be due to a beneficial effect on asthma-related serious adverse events. There was no difference compared to placebo in adverse events leading to discontinuation with mepolizumab or reslizumab, but significantly more discontinued benralizumab than placebo, although the absolute numbers were small (36/1599 benralizumab versus 9/998 placebo).Mepolizumab, reslizumab and benralizumab all markedly reduced blood eosinophils, but benralizumab resulted in almost complete depletion, whereas a small number remained with mepolizumab and reslizumab. The implications for efficacy and/or adverse events are unclear.
AUTHORS' CONCLUSIONS
Overall our study supports the use of anti-IL-5 treatments as an adjunct to standard of care in people with severe eosinophilic asthma and poor control. These treatments roughly halve the rate of asthma exacerbations in this population. There is limited evidence for improved HRQoL scores and lung function, which may not meet clinically detectable levels. There were no safety concerns regarding mepolizumab or reslizumab, and no excess serious adverse events with benralizumab, although there remains a question over adverse events significant enough to prompt discontinuation.Further research is needed on biomarkers for assessing treatment response, optimal duration and long-term effects of treatment, risk of relapse on withdrawal, non-eosinophilic patients, children (particularly under 12 years), and comparing anti-IL-5 treatments to each other and, in people eligible for both, to anti-immunoglobulin E. For benralizumab, future studies should closely monitor rates of adverse events prompting discontinuation.
Topics: Adolescent; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Asthma; Child; Disease Progression; Humans; Injections, Intravenous; Injections, Subcutaneous; Interleukin-5; Quality of Life; Randomized Controlled Trials as Topic; Receptors, Interleukin-5
PubMed: 28933516
DOI: 10.1002/14651858.CD010834.pub3 -
Resuscitation Apr 2020To perform a systematic review of the literature on intravenous (IV) vs. intraosseous (IO) administration of drugs during cardiac arrest in order to inform an update of... (Review)
Review
AIM
To perform a systematic review of the literature on intravenous (IV) vs. intraosseous (IO) administration of drugs during cardiac arrest in order to inform an update of international guidelines.
METHODS
The review was performed according to PRISMA guidelines and registered on PROSPERO. Medline, Embase and Evidence-Based Medicine Reviews were searched on December 17, 2019 for studies comparing IV to IO administration of drugs. The population included neonatal, paediatric, and adult patients with cardiac arrest. Two investigators reviewed each search for study relevance, extracted data, and assessed the risk of bias of individual studies. Meta-analyses were performed for studies without a critical risk of bias. Certainty of evidence was evaluated using GRADE.
RESULTS
We included six observational studies comparing IV to IO administration of drugs and two randomized trials assessing the effect of specific drugs in subgroups related to IV vs. IO administration. All studies included adult out-of-hospital cardiac arrest patients. No studies were identified in neonatal or paediatric patients. The risk of bias for the observational studies was overall assessed as critical or serious, with confounding and selection bias being the primary sources of bias. The meta-analyses excluding studies with a critical risk of bias favoured IV access for all outcomes. Using GRADE, the certainty of evidence was judged at very low. Subgroup analyses of the two randomized trials demonstrated no statistically significant interactions between the route of access and study drugs on outcomes. However, these trials were underpowered to assess such interactions.
CONCLUSIONS
We identified a limited number of studies comparing IV vs. IO administration of drugs during cardiac arrest. Pooled results from four observational studies favoured IV access with very low certainty of evidence. From the subgroup analyses of two randomized clinical trials, there was no statistically significant interaction between the route of access and study drug on outcomes.
Topics: Administration, Intravenous; Adult; Child; Humans; Infant, Newborn; Infusions, Intraosseous; Out-of-Hospital Cardiac Arrest; Pharmaceutical Preparations
PubMed: 32142750
DOI: 10.1016/j.resuscitation.2020.02.025 -
Neuroscience and Biobehavioral Reviews Jul 2017There is growing interest in the role of the oxytocin system in social cognition and behavior. Peripheral oxytocin concentrations are regularly used to approximate... (Meta-Analysis)
Meta-Analysis Review
There is growing interest in the role of the oxytocin system in social cognition and behavior. Peripheral oxytocin concentrations are regularly used to approximate central concentrations in psychiatric research, however, the validity of this approach is unclear. Here we conducted a pre-registered systematic search and meta-analysis of correlations between central and peripheral oxytocin concentrations. A search of databases yielded 17 eligible studies, resulting in a total sample size of 516 participants and subjects. Overall, a positive association between central and peripheral oxytocin concentrations was revealed [r=0.29, 95% CI (0.14, 0.42), p<0.0001]. This association was moderated by experimental context [Q(4), p=0.003]. While no association was observed under basal conditions (r=0.08, p=0.31), significant associations were observed after intranasal oxytocin administration (r=0.66, p<0.0001), and after experimentally induced stress (r=0.49, p=0.001). These results indicate a coordination of central and peripheral oxytocin release after stress and after intranasal administration. Although popular, the approach of using peripheral oxytocin levels to approximate central levels under basal conditions is not supported by the present results.
Topics: Administration, Intranasal; Humans; Oxytocin; Social Behavior
PubMed: 28442403
DOI: 10.1016/j.neubiorev.2017.04.017 -
The Cochrane Database of Systematic... Mar 2015Many patients with cancer experience moderate to severe pain that requires treatment with strong analgesics. Buprenorphine, fentanyl and morphine are examples of strong... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many patients with cancer experience moderate to severe pain that requires treatment with strong analgesics. Buprenorphine, fentanyl and morphine are examples of strong opioids used for cancer pain relief. However, strong opioids are ineffective as pain treatment in all patients and are not well-tolerated by all patients. The aim of this Cochrane review is to assess whether buprenorphine is associated with superior, inferior or equal pain relief and tolerability compared to other analgesic options for patients with cancer pain.
OBJECTIVES
To assess the effectiveness and tolerability of buprenorphine for pain in adults and children with cancer.
SEARCH METHODS
We searched CENTRAL (the Cochrane Library) issue 12 or 12 2014, MEDLINE (via OVID) 1948 to 20 January 2015, EMBASE (via OVID) 1980 to 20 January 2015, ISI Web of Science (SCI-EXPANDED & CPCI-S) to 20 January 2015, ISI BIOSIS 1969 to 20 January 2015. We also searched ClinicalTrials.gov (http://clinicaltrials.gov/; metaRegister of Controlled Trials (mRCT) (http://www.controlled-trials.com/mrct/), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal (http://apps.who.int/trialsearch/) and the Proceedings of the Congress of the European Federation of International Association for the Study of Pain (IASP; via European Journal of Pain Supplements) on 16 February 2015. We checked the bibliographic references of identified studies as well as relevant studies and systematic reviews to find additional trials not identified by the electronic searches. We contacted authors of included studies for other relevant studies.
SELECTION CRITERIA
We included randomised controlled trials, with parallel-group or crossover design, comparing buprenorphine (any formulation and any route of administration) with placebo or an active drug (including buprenorphine) for cancer background pain in adults and children.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data pertaining to study design, participant details (including age, cancer characteristics, previous analgesic medication and setting), interventions (including details about titration) and outcomes, and independently assessed the quality of the included studies according to standard Cochrane methodology. As it was not feasible to meta-analyse the data, we summarised the results narratively. We assessed the overall quality of the evidence for each outcome using the GRADE approach.
MAIN RESULTS
In this Cochrane review we identified 19 relevant studies including a total of 1421 patients that examined 16 different intervention comparisons.Of the studies that compared buprenorphine to another drug, 11 studies performed comparative analyses between the randomised groups, and five studies found that buprenorphine was superior to the comparison treatment. Three studies found no differences between buprenorphine and the comparison drug, while another three studies found treatment with buprenorphine to be inferior to the alternative treatment in terms of the side effects profile or patients preference/acceptability.Of the studies that compared different doses or formulations/routes of administration of buprenorphine, pain intensity ratings did not differ significantly between intramuscular buprenorphine and buprenorphine suppository. However, the average severity of dizziness, nausea, vomiting and adverse events as a total were all significantly higher in the intramuscular group relatively to the suppository group (one study).Sublingual buprenorphine was associated with faster onset of pain relief compared to subdermal buprenorphine, with similar duration analgesia and no significant differences in adverse event rates reported between the treatments (one study).In terms of transdermal buprenorphine, two studies found it superior to placebo, whereas a third study found no difference between placebo and different doses of transdermal buprenorphine.The studies that examined different doses of transdermal buprenorphine did not report a clear dose-response relationship.The quality of this evidence base was limited by under-reporting of most bias assessment items (e.g., the patient selection items), by small sample sizes in several included studies, by attrition (with data missing from 8.2% of the enrolled/randomised patients for efficacy and from 14.6% for safety) and by limited or no reporting of the expected outcomes in a number of cases. The evidence for all the outcomes was very low quality.
AUTHORS' CONCLUSIONS
Based on the available evidence, it is difficult to say where buprenorphine fits in the treatment of cancer pain with strong opioids. However, it might be considered to rank as a fourth-line option compared to the more standard therapies of morphine, oxycodone and fentanyl, and even there it would only be suitable for some patients. However, palliative care patients are often heterogeneous and complex, so having a number of analgesics available that can be given differently increases patient and prescriber choice. In particular, the sublingual and injectable routes seemed to have a more definable analgesic effect, whereas the transdermal route studies left more questions.
Topics: Administration, Cutaneous; Administration, Oral; Administration, Sublingual; Adult; Analgesics, Opioid; Buprenorphine; Child; Humans; Neoplasms; Pain; Randomized Controlled Trials as Topic
PubMed: 25826743
DOI: 10.1002/14651858.CD009596.pub4 -
Journal of Controlled Release :... Aug 2022Although curcumin is globally recognized for its health benefits, its clinical application has been restricted by its poor aqueous solubility and stability. To overcome... (Review)
Review
Although curcumin is globally recognized for its health benefits, its clinical application has been restricted by its poor aqueous solubility and stability. To overcome these limitations, nanocarrier-based drug delivery systems (NDS) are one of the most effective approaches being extensively explored over the last few decades to improve curcumin's physicochemical and pharmacological effects. Various NDS could provide productive platforms for addressing the formulation challenge of curcumin, but evidence of such systems has not been summarized. This study aimed to systematically review current evidence of lipid and polymer-based NDS for an oral delivery of curcumin focusing on in vivo models and clinical studies. Among the 48 included studies, 3 studies were randomized controlled clinical trials, while 45 studies were animal models. To date, only five curcumin NDS have been studied in healthy volunteers: γ-cyclodextrin, phytosome, liposome, microemulsion and solid dispersion, while most curcumin NDS have been studied in animal models. Most included studies found that NDS could increase oral bioavailability of curcumin as compared to free curcumin. In conclusion, this systematic review showed evidence of the positive effect of NDS for enhancement of oral bioavailability of curcumin. EXECUTIVE SUMMARY: Curcumin is globally recognized for its health benefits, but its clinical application has been limited by its poor aqueous solubility and stability, which causes poor absorption in the gastrointestinal tract (GI tract) via oral administration. Nanocarrier-based drug delivery systems (NDS) are considered as a productive platform to solve the formulation challenge of curcumin, but evidence of such systems has not been summarized. This study aimed to systematically review current evidence of lipid and polymer-based NDS for an oral delivery of curcumin focusing on in vivo models and clinical studies. Overall, most studies found that all studied NDS could increase the absorption of curcumin as compared to free curcumin. Curcumin was rapidly absorbed and exhibited a long residence time after oral administration of curcumin NDS. In summary, this systematic review showed positive impacts of NDS for enhancement of oral absorption of curcumin.
Topics: Administration, Oral; Animals; Biological Availability; Curcumin; Drug Delivery Systems; Lipids; Polymers; Solubility
PubMed: 35654170
DOI: 10.1016/j.jconrel.2022.05.048 -
Journal of Orthopaedic Surgery and... May 2023Platelet-rich plasma (PRP) injection for ankle osteoarthritis (OA) treatment showed contradictory results. This review was aimed to pool individual studies which... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Platelet-rich plasma (PRP) injection for ankle osteoarthritis (OA) treatment showed contradictory results. This review was aimed to pool individual studies which assessed the efficacy of PRP for ankle OA treatment.
METHODS
This study was conducted following the preferred report items of systematic review and meta-analysis guideline. PubMed and Scopus were searched up to January 2023. Meta-analysis, or individual randomised controlled trial (RCT), or observational studies were included if they involved ankle OA with aged ≥ 18 years, compared before-after receiving PRP, or PRP with other treatments, and reported visual analog scale (VAS) or functional outcomes. Selection of eligible studies and data extraction were independently performed by two authors. Heterogeneity test using Cochrane Q test and the I-statistic were assessed. Standardised (SMD) or unstandardised mean difference (USMD) and 95% confidence interval (CI) were estimated and pooled across studies.
RESULTS
Three studies from meta-analysis and two individual studies were included, which consisted of one RCT and four before-after studies with 184 ankle OAs and 132 PRP. The average age was 50.8-59.3 years, and 25-60% of PRP injected cases were male. The number of primary ankle OA was accounted to 0-100%. When compared to before treatment, PRP significantly reduced VAS and functional score at 12 weeks with pooled USMD of - 2.80, 95% CI - 3.91, - 2.68; p < 0.001 (Q = 82.91, p < 0.001; I 96.38%), and pooled SMD of 1.73, 95% CI 1.37, 2.09; p < 0.001 (Q = 4.87, p = 0.18; I 38.44%), respectively.
CONCLUSION
PRP may beneficially improve pain and functional scores for ankle OA in a short-term period. Its magnitude of improvement seems to be similar to placebo effects from the previous RCT. A large-scale RCT with proper whole blood and PRP preparation processes is required to prove treatment effects. Trial registration PROSPERO number CRD42022297503.
Topics: Male; Humans; Middle Aged; Female; Ankle; Osteoarthritis; Pain; Injections; Platelet-Rich Plasma; Treatment Outcome; Injections, Intra-Articular; Hyaluronic Acid; Osteoarthritis, Knee
PubMed: 37208754
DOI: 10.1186/s13018-023-03828-z -
Substance Use & Misuse 2024Knowledge of the cardiovascular and respiratory effects of cannabis use by route of administration is unclear. This evidence is necessary to increase clinical and...
Knowledge of the cardiovascular and respiratory effects of cannabis use by route of administration is unclear. This evidence is necessary to increase clinical and public health awareness given the recent trend in cannabis legalization, normalization, and surge in the availability and usage of various forms of cannabis products. Search was conducted in Web of Science, ProQuest, Psych INFO, Scopus, Embase, and Medline databases, and subsequently in the references of retrieved articles. Peer-reviewed articles published between 2009 and 2023, that reported on cardiovascular and respiratory effects of cannabis use by route of administration were included. Studies with no report of the route of administration and combined use of other illicit substances were excluded. The review was guided by Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Of the 1873 articles retrieved, 42 met inclusion criteria encompassing six case reports, 21 reviews, and 15 empirical studies. Four administration routes were identified: smoking, vaping, oral ingestion, and dabbing. Smoking was the most common route of administration and was associated with both respiratory effects, such as bronchitis, dyspnea, and chronic obstructive lung disease, and cardiovascular effects including tachycardia, ventricular arrhythmias, and myocardial infarction. Cannabis edibles were associated with minimal respiratory effects. Tachycardia was the most common cardiovascular effect and was associated with all routes of administration. Cannabis use does cause cardiovascular and respiratory effects, but the conclusion remains tentative of the cardiovascular and respiratory effects by route of administration due to methodological limitations of the studies.
Topics: Humans; Marijuana Smoking; Vaping; Cannabis; Drug Administration Routes; Cardiovascular System
PubMed: 38644600
DOI: 10.1080/10826084.2024.2341317 -
The Journal of Dermatology Apr 2023Intra- and transdermal administration of substances via percutaneous injection is effective but considered painful, and inconvenient in addition to bringing forth... (Review)
Review
Intra- and transdermal administration of substances via percutaneous injection is effective but considered painful, and inconvenient in addition to bringing forth biohazardous waste material. In contrast to injection, topical drug application, which includes ointments, creams and lotions, increases the local drug load. Moreover, it has reduced side effects compared to systemic administration. However, the epidermis poses a barrier to high molecular weight substances, limiting the delivery efficiency. Dissolving microneedles (DMN) are hydrophilic, mostly polymer-based constructs that are capable of skin penetration and were developed to provide painless and direct dermal drug delivery. This systematic review provides a comprehensive overview of the available clinical evidence for the use of DMN to treat various skin conditions. According to the PRISMA statement, a systematic search for articles on the use of DMN for dermatological indications was conducted on three different databases (Pubmed, Embase, and the Cochrane library). Only human clinical trials were considered. Qualitative assessment was done by two separate reviewers using the Cochrane risk of bias (RoB 2) and Chambers' criteria assessment tools. The search yielded 1090 articles. After deduplication and removal of ineligible records, 889 records were screened on title and abstract. Full text screening was done for 18 articles and ultimately 17 articles were included of which 15 were randomized controlled trials and two were case series. The quality assessment showed that the majority of included studies had low to no risk of bias. Clinical data supports that DMN are an excellent, effective, and pain free drug delivery method for multiple dermatological disorders including skin aging, hyperpigmentation, psoriasis, warts, and keloids by supplying a painless and effective vehicle for intradermal/intralesional drug administration. Microneedle technology provides a promising non- to minimally-invasive alternative to percutaneous injection.
Topics: Humans; Microinjections; Skin; Administration, Cutaneous; Drug Delivery Systems; Epidermis; Needles; Pain
PubMed: 36700529
DOI: 10.1111/1346-8138.16732 -
The Cochrane Database of Systematic... Jan 2016Ovarian cancer tends to be chemosensitive and confine itself to the surface of the peritoneal cavity for much of its natural history. These features have made it an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ovarian cancer tends to be chemosensitive and confine itself to the surface of the peritoneal cavity for much of its natural history. These features have made it an obvious target for intraperitoneal (IP) chemotherapy. Chemotherapy for ovarian cancer is usually given as an intravenous (IV) infusion repeatedly over five to eight cycles. Intraperitoneal chemotherapy is given by infusion of the chemotherapeutic agent directly into the peritoneal cavity. There are biological reasons why this might increase the anticancer effect and reduce some systemic adverse effects in comparison to IV therapy.
OBJECTIVES
To determine if adding a component of the chemotherapy regime into the peritoneal cavity affects overall survival, progression-free survival, quality of life (QOL) and toxicity in the primary treatment of epithelial ovarian cancer.
SEARCH METHODS
We searched the Gynaecological Cancer Review Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2011, MEDLINE (1951 to May 2011) and EMBASE (1974 to May 2011). We updated these searches in February 2007, August 2010, May 2011 and September 2015. In addition, we handsearched and cascade searched the major gynaecological oncology journals up to May 2011.
SELECTION CRITERIA
The analysis was restricted to randomised controlled trials (RCTs) assessing women with a new diagnosis of primary epithelial ovarian cancer, of any FIGO stage, following primary cytoreductive surgery. Standard IV chemotherapy was compared with chemotherapy that included a component of IP administration.
DATA COLLECTION AND ANALYSIS
We extracted data on overall survival, disease-free survival, adverse events and QOL and performed meta-analyses of hazard ratios (HR) for time-to-event variables and relative risks (RR) for dichotomous outcomes using RevMan software.
MAIN RESULTS
Nine randomised trials studied 2119 women receiving primary treatment for ovarian cancer. We considered six trials to be of high quality. Women were less likely to die if they received an IP component to chemotherapy (eight studies, 2026 women; HR = 0.81; 95% confidence interval (CI): 0.72 to 0.90). Intraperitoneal component chemotherapy prolonged the disease-free interval (five studies, 1311 women; HR = 0.78; 95% CI: 0.70 to 0.86). There was greater serious toxicity with regard to gastrointestinal effects, pain, fever and infection but less ototoxicity with the IP than the IV route.
AUTHORS' CONCLUSIONS
Intraperitoneal chemotherapy increases overall survival and progression-free survival from advanced ovarian cancer. The results of this meta-analysis provide the most reliable estimates of the relative survival benefits of IP over IV therapy and should be used as part of the decision making process. However, the potential for catheter related complications and toxicity needs to be considered when deciding on the most appropriate treatment for each individual woman. The optimal dose, timing and mechanism of administration cannot be addressed from this meta-analysis. This needs to be addressed in the next phase of clinical trials.
Topics: Antineoplastic Agents; Disease-Free Survival; Female; Humans; Induction Chemotherapy; Infusions, Intravenous; Infusions, Parenteral; Ovarian Neoplasms; Randomized Controlled Trials as Topic
PubMed: 26755441
DOI: 10.1002/14651858.CD005340.pub4