title: Potential impact of mTOR inhibitors on cervical squamous cell carcinoma: A systematic review.
abstract: The aim of the present systematic review was to analyze the potential impact of mammalian target of rapamycin (mTOR) inhibitors on the treatment of cervical squamous cell carcinoma (CSCC). A systematic literature search was conducted in PubMed, PMC, Scopus, Cochrane Library, LILACS, Web of Science, Google Scholar and ScienceDirect on January 19, 2015, without time and language restrictions. Studies that evaluated women of any age with CSCC and who received mTOR inhibitors alone or in association with other treatments were considered. Randomized and non-randomized clinical trials were included, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was followed. Selected studies were methodologically appraised according to the Grades of Recommendation, Assessment, Development and Evaluation method to assess the quality of evidence. Of 642 identified citations, 43 studies were fully reviewed; however, only 3 studies met the inclusion criteria and were used for qualitative analysis. Of these, two studies were phase 1 and one was a phase 2 clinical trial. The studies included were not conclusive with regard to the association between mTOR inhibitor treatment and cervical cancer. The main analysis of secondary endpoints revealed that individuals treated with other drugs in association with mTOR inhibitors achieved partial responses (15.4-33.3%) or stable disease (17.6-28%). Treatment with mTOR inhibitors in general was well tolerated in patients with metastatic disease. The predominant toxicities were grade 1 and 2. The phase 1 trials included in this review demonstrated that mTOR inhibitor treatments are feasible and safe. However, the currently available evidence is insufficient to determine the effect of mTOR inhibitors on CSCC, and further investigation in high-quality, randomized clinical trials is required.
authors.affiliation: Oral Histopathology Laboratory, School of Health Sciences, University of Brasília, Brasília, Federal District 70910-900, Brazil; Oncology Center, Hospital Sírio-Libanês, Brasília, Federal District 71635-610, Brazil.
authors.forename: Daniele Xavier
authors.initials: DX
authors.lastname: Assad
authors.affiliation: Oral Histopathology Laboratory, School of Health Sciences, University of Brasília, Brasília, Federal District 70910-900, Brazil.
authors.forename: Silvia Taveira
authors.initials: ST
authors.lastname: Elias
authors.affiliation: Department of Clinical Research, National Institute of Cancer, Rio de Janeiro 20220-410, Brazil.
authors.forename: Andréia Cristina
authors.initials: AC
authors.lastname: Melo
authors.affiliation: Department of Clinical Research, National Institute of Cancer, Rio de Janeiro 20220-410, Brazil; National Clinical Cancer Research Network, Ministry of Health, Brasília, Federal District 70058-900, Brazil; Department of Clinical Research, D'or Institute for Research, Rio de Janeiro 22281-100, Brazil.
authors.forename: Carlos Gil
authors.initials: CG
authors.lastname: Ferreira
authors.affiliation: Department of Dentistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina 88036-800, Brazil; Department of Dentistry, University of Alberta, Edmonton, Alberta T6G 1C9, Canada.
authors.forename: Graziela
authors.initials: G
authors.lastname: De Luca Canto
authors.affiliation: Oral Histopathology Laboratory, School of Health Sciences, University of Brasília, Brasília, Federal District 70910-900, Brazil.
authors.forename: Eliete Neves Silva
authors.initials: EN
authors.lastname: Guerra
keywords: cervical cancer; evidence-based medicine; mammalian target of rapamycin inhibitors; systematic review