Phase II study of temsirolimus (CCI-779) in women with recurrent, unresectable, locally advanced or metastatic carcinoma of the cervix. A trial of the NCIC Clinical Trials Group (NCIC CTG IND 199)

Tinker, Anna V.; Ellard, Susan; Welch, Stephen; Moens, Francois; Allo, Ghassan; Tsao, Ming‐Sound; Squire, Jeremy A.; Tu, Dongsheng; Eisenhauer, Elizabeth; Mackay, Helen

doi:10.1016/j.ygyno.2013.05.008

Cited by 88 publications

(61 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the study by Moroney et al (60), liposomal doxorubicin was also included, making this analysis further complicated. The other important limitation is that only the phase 2 trial included >20 CSCC patients, but this study reported no responses to temsirolimus in CSCC patients (62). The phase 1 studies included ≤10 CSCC patients (60,61).…”

Section: Discussionmentioning

confidence: 92%

“…The present review identified only two phase 1 (60,61) and one phase 2 (62) clinical trials that met the inclusion criteria. All studies were non-randomized and included treatment with temsirolimus as the mTOR inhibitor agent.…”

Section: Discussionmentioning

confidence: 99%

“…This process excluded 40 studies . Finally, 3 studies were selected (60)(61)(62). A flow chart detailing the process of identification, inclusion and exclusion of studies is shown in Fig.…”

Section: Study Selectionmentioning

confidence: 99%

“…The selected studies were conducted in two countries: The USA (60,61) and Canada (62). All 3 studies were published recently, in 2011 (60), 2013 (62), 2014 (61), and all were written in English.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…The GRADE approach (19) was used to assess the quality of evidence of the included studies, as outlined in Table II. All studies were categorized as having a low quality level of evidence (60)(61)(62). All had serious issues with regard to the design, none had control groups, and all lacked blinding.…”

Section: Study Characteristicsmentioning

confidence: 99%

See 4 more Smart Citations

Potential impact of mTOR inhibitors on cervical squamous cell carcinoma: A systematic review

et al. 2016

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

“…This process excluded 40 studies . Finally, 3 studies were selected (60)(61)(62). A flow chart detailing the process of identification, inclusion and exclusion of studies is shown in Fig.…”

Section: Study Selectionmentioning

confidence: 99%

Section: Study Characteristicsmentioning

confidence: 99%

Section: Study Characteristicsmentioning

confidence: 99%

See 3 more Smart Citations

Potential impact of mTOR inhibitors on cervical squamous cell carcinoma: A systematic review

et al. 2016

View full text Add to dashboard Cite

show abstract

The Potential Value of the PI3K/Akt/mTOR Signaling Pathway for Assessing Prognosis in Cervical Cancer and as a Target for Therapy

Bahrami

Hasanzadeh

Hassanian

et al. 2017

J of Cellular Biochemistry

103

View full text Add to dashboard Cite

Cervical cancer is a common gynecological cancer and a leading cause of cancer-related death in women globally. There is a need for the identification of prognostic and predictive biomarker for risk stratification. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is often dysregulated in cervical cancer, indicating that it may be a potential therapeutic target in the treatment of this malignancy, and could perhaps be used as a novel biomarker in the assessment of risk of developing cervical cancer. We aimed to provide an overview of the potential applications of the PI3K/Akt/mTOR pathway as biomarker for risk stratification, in predicting the prognosis of cervical cancer, and for developing new therapeutic approaches in patients with cervical cancer. J. Cell. Biochem. 118: 4163-4169, 2017. © 2017 Wiley Periodicals, Inc.

show abstract

Olive Oil‐derived Oleocanthal as Potent Inhibitor of Mammalian Target of Rapamycin: Biological Evaluation and Molecular Modeling Studies

Khanfar

Bardaweel

Akl

et al. 2015

Phytotherapy Research

View full text Add to dashboard Cite

The established anticancer and neuroprotective properties of oleocanthal combined with the reported role of mammalian target of rapamycin (mTOR) in cancer and Alzheimer’s disease development encouraged us to examine the possibility that oleocanthal inhibits mTOR. To validate this hypothesis, we docked oleocanthal into the adenosine triphosphate binding pocket of a close mTOR protein homologue, namely, PI3K-γ. Apparently, oleocanthal shared nine out of ten critical binding interactions with a potent dual PIK3-γ/mTOR natural inhibitor. Subsequent experimental validation indicated that oleocanthal indeed inhibited the enzymatic activity of mTOR with an IC50 value of 708 nM. Oleocanthal inhibits the growth of several breast cancer cell lines at low micromolar concentration in a dose-dependent manner. Oleocanthal treatment caused a marked downregulation of phosphorylated mTOR in metastatic breast cancer cell line (MDA-MB-231). These results strongly indicate that mTOR inhibition is at least one of the factors of the reported anticancer and neuroprotective properties of oleocanthal.

show abstract

Phase II study of temsirolimus (CCI-779) in women with recurrent, unresectable, locally advanced or metastatic carcinoma of the cervix. A trial of the NCIC Clinical Trials Group (NCIC CTG IND 199)

Cited by 88 publications

References 26 publications

Potential impact of mTOR inhibitors on cervical squamous cell carcinoma: A systematic review

Potential impact of mTOR inhibitors on cervical squamous cell carcinoma: A systematic review

The Potential Value of the PI3K/Akt/mTOR Signaling Pathway for Assessing Prognosis in Cervical Cancer and as a Target for Therapy

Olive Oil‐derived Oleocanthal as Potent Inhibitor of Mammalian Target of Rapamycin: Biological Evaluation and Molecular Modeling Studies

Contact Info

Product

Resources

About