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The Cochrane Database of Systematic... Nov 2011Ovarian 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 and May 2011. In addition, we handsearched and cascade searched the major gynaecological oncology journals.
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; Infusions, Intravenous; Infusions, Parenteral; Ovarian Neoplasms; Randomized Controlled Trials as Topic
PubMed: 22071822
DOI: 10.1002/14651858.CD005340.pub3 -
Annals of Family Medicine 2005We wanted to determine whether metformin is an effective medication for treatment of overweight or obese adults who do not have diabetes mellitus or polycystic ovary... (Meta-Analysis)
Meta-Analysis
PURPOSE
We wanted to determine whether metformin is an effective medication for treatment of overweight or obese adults who do not have diabetes mellitus or polycystic ovary syndrome (PCOS).
METHODS
We searched MEDLINE (1966-2003), EMBASE (1986-2003), Allied and Complementary Medicine Database (1985-2003), International Pharmaceutical Abstracts (1970-2003), the Cochrane Library, American College of Physicians Journal Club, Database of Abstracts of Reviews of Effects, Cochrane Controlled Trials Register, MEDLINE In-Process & Other Non-Indexed Citations, reference lists of retrieved articles, and articles by selected authors and pharmaceutical manufacturers. Inclusion criteria were being obese or overweight determined by a BMI of 25 kg/m2 or greater or waist-to-hip ratio (WHR) of more than 0.8, metformin use, and aged 18 years or older. Exclusion criteria were a diagnosis of diabetes mellitus, polycystic ovarian syndrome or descriptors of polycystic ovarian syndrome, human immunodeficiency virus infection, and concomitant antipsychotic medications. Trials were graded on an 11-point Jadad scale. Only randomized controlled and blinded trials were accepted. Two reviewers independently extracted data from each trial. Primary outcomes measured were changes in BMI, WHR, and weight.
RESULTS
Fifty-seven potentially relevant studies were initially identified; 48 were excluded because of lack of randomization, lack of blinding, failure to meet inclusion or exclusion criteria, inaccessible outcomes, or improper study design. Nine clinical trials met criteria for validity assessment. Four studies used the parameter of waist-to-hip ratio, 3 studies included BMI, and 8 used weight. Two of the 9 studies showed a small reduction in WHR.
CONCLUSION
Insufficient evidence exists for the use of metformin as treatment of overweight or obese adults who do not have diabetes mellitus or polycystic ovary syndrome. Further studies are needed to answer this clinical question.
Topics: Adult; Humans; Metformin; Obesity; Overweight; Randomized Controlled Trials as Topic
PubMed: 16189063
DOI: 10.1370/afm.343