Importance
Chemotherapy may result in a detrimental effect on ovarian function and fertility in premenopausal women undergoing curative treatment for early breast cancer (EBC). For this subgroup of patients, a careful consideration for techniques to minimize this risk should be given and the role of gonadotropin-releasing hormone agonists (GnRHa) for protection of ovarian function is not fully resolved.
Objective
To determine efficacy of GnRHa administered concurrently with chemotherapy for ovarian function preservation.
Data sources
The search for studies published between 1975 and March/2015 encompassed PubMed, SCOPUS and Cochrane databases, as well as ASCO Annual Meeting and San Antonio Breast Cancer Symposium abstracts.
Study selection
Prospective, randomized, controlled trials addressing the role of ovarian suppression with GnRHa in preventing early ovarian dysfunction in premenopausal women undergoing treatment for EBC were selected.
Data extraction and synthesis
Data extraction was performed independently by two authors. The methodology and the risk of bias were assessment based on the description of randomization method, withdrawals and blinding process.
Main Outcomes Measures
Rate of resumption of regular menses after a minimal follow-up period of 6 months following chemotherapy was used as surrogate to assess the incidence of ovarian dysfunction. Additional secondary outcomes included hormone levels and number of pregnancies. Risk ratio estimates were calculated based on the number of evaluable patients. Analyses were conducted using a random effect model.
Results
Seven studies were selected, totaling 1047 randomized patients (856 evaluable patients).. The use of GnRHa was associated with a higher rate of recovery of regular menses after 6 months (OR = 2.41; 95% CI 1.40–4.15; p= 0. 002) and at least 12 months (OR 1.85; 95% CI 1.33–2.59; p = 0.0003) following last chemotherapy cycle. The use of GnRHa was also associated with a higher number of pregnancies (OR 1.85; 95% IC 1.02–3.36; p=0.04), although this outcome was not uniformly reported.
Conclusions and Relevance
GnRHa given with chemotherapy resulted in increased rates of recovery of regular menses and should be considered an option for ovarian function preservation in young women undergoing treatment for EBC. Additional outcomes related to ovarian function and fertility need to be further investigated.
BackgroundBevacizumab has an important role in first-line treatment of metastatic colorectal cancer. However, clinical trials studying its effect have involved distinct chemotherapy regimens with divergent results. The aim of this meta-analysis is to gather current data and evaluate not only the efficacy of bevacizumab, but also the impact of divergent backbone regimens.MethodsA wide search of randomized clinical trials using bevacizumab in first-line metastatic colorectal cancer was performed in Embase, MEDLINE, LILACS and Cochrane databases. Meeting presentations and abstracts were also investigated. The resulting data were examined and included in the meta-analysis according to the type of regimen.ResultsSix trials, totaling 3060 patients, were analyzed. There was an advantage to using bevacizumab for overall survival (OS) and progression-free survival (PFS) (HR = 0.84; CI: 0.77-0.91; P < 0.00001 and HR = 0.72; CI: 0.66-0.78; P < 0.00001, respectively). However, heterogeneity of results was very high for both outcomes, and subgroup analyses supported the OS advantage with bevacizumab restricted to irinotecan-based regimens. Infusional fluorouracil subsets involved a minor proportion, and did not demonstrate statistical benefit in PFS or OS. Regarding toxicity, higher rates of grades 3-4 hypertension, bleeding, thromboembolic events and proteinuria were uniformly observed with bevacizumab, leading to increased treatment interruptions (HR = 1.47; P = 0.0004).ConclusionsBevacizumab has efficacy in first-line treatment of advanced colorectal cancer, but the current data are insufficient to support efficacy in all regimens, especially infusional fluorouracil regimens, like FOLFIRI and FOLFOX.
NK1R antagonists increased CINV control in the acute, delayed, and overall phases. They are effective for both moderately and highly emetogenic chemotherapy regimens. Their use might be associated with increased infection rates; however, additional appraisal of specific data from RCTs is needed.
SummaryDefinitions for a 4-stage continuum of HIV care were standardized and applied to HIV surveillance and national cohort data in 11 European Union countries. These countries are nearing the UNAIDS 90-90-90 target, although reducing the proportion undiagnosed remains challenging.
From all available possibilities for the prevention of HFS, celecoxib appears to be the most promising, with statistically significant results. Larger, multicentric studies are required to reinforce this finding.
Lymphogranuloma venereum, caused by the L serovars of Chlamydia trachomatis, emerged in Europe in 2003 and a series of outbreaks were reported in different countries. The infection presents as a severe proctitis in men who have sex with men, many of whom are co-infected with HIV and other sexually transmitted infections. This paper reviews the number of cases reported over a five year period, from 2003 to 2008, from countries that were part of the European Surveillance of Sexually Transmitted Infections (ESSTI) network. Reports were received from Belgium,
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