PMID- 25635371
OWN - NLM
STAT- MEDLINE
DCOM- 20150417
LR  - 20211203
IS  - 1532-4192 (Electronic)
IS  - 0735-7907 (Linking)
VI  - 33
IP  - 3
DP  - 2015 Mar
TI  - Incidence and risk of high-grade stomatitis with mTOR inhibitors in cancer 
      patients.
PG  - 70-7
LID - 10.3109/07357907.2014.1001893 [doi]
AB  - BACKGROUND: Inhibitors of the mammalian target of rapamycin (mTOR) pathway 
      including everolimus and temsirolimus have been used extensively in cancer 
      patients. Their use is associated with stomatitis, an adverse event resulting in 
      morbidity and treatment interruptions or discontinuation. This study was 
      conducted to determine the overall incidence and risk of stomatitis in cancer 
      patients treated with the mTOR inhibitors by a meta-analysis of randomized 
      controlled clinical trials (RCTs). PATIENTS AND METHODS: Databases from PubMed 
      and abstracts presented at the American Society of Clinical Oncology annual 
      meetings up to October 2013 were searched for relevant studies. Eligible studies 
      included RCTs using everolimus and temsirolimus at approved doses in cancer 
      patients. Summary incidences, relative risks (RR), and 95% confidence intervals 
      (CI) were calculated using a random- or fixed-effects model depending on the 
      heterogeneity of the included trials. RESULTS: A total of 11 RCTs with 4,752 
      patients (mTORs: 2,725, controls: 2,027) with a variety of solid tumors were 
      included in the analysis. The incidences of all-grade (grade 1-4) and high-grade 
      stomatitis (grade 3-4) were 33.5% (95% CI: 21.9-47.6%) and 4.1% (95% CI: 
      2.6-6.3%), respectively. The incidence of high-grade stomatitis significantly 
      varied with tumor types (p=.004), and mTOR inhibitors (temsirolimus vs. 
      everolimus, p<.001). In comparison with controls, mTOR inhibitors significantly 
      increased the risk for developing all-grade stomatitis (RR: 4.04, 95% CI: 
      3.13-5.22, p<.001) and high-grade stomatitis (RR: 8.84, 95% CI: 4.07-19.22, 
      p<.001). CONCLUSIONS: The mTOR inhibitors everolimus and temsirolimus 
      significantly increased the risk of high-grade stomatitis in cancer patients. 
      Efforts towards the prevention, treatment, and identification of individuals at 
      risk may allow for improved quality of life and consistent dosing.
FAU - Shameem, Raji
AU  - Shameem R
AD  - Department of Hematology/Oncology, Fox Chase Cancer Center , Philadelphia, PA , 
      USA , 1.
FAU - Lacouture, Mario
AU  - Lacouture M
FAU - Wu, Shenhong
AU  - Wu S
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
DEP - 20150130
PL  - England
TA  - Cancer Invest
JT  - Cancer investigation
JID - 8307154
RN  - 624KN6GM2T (temsirolimus)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Everolimus
MH  - Humans
MH  - Incidence
MH  - Neoplasms/*drug therapy
MH  - Randomized Controlled Trials as Topic
MH  - Risk Factors
MH  - Sirolimus/adverse effects/*analogs & derivatives
MH  - Stomatitis/*chemically induced
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
OTO - NOTNLM
OT  - cancer
OT  - everolimus
OT  - mTOR inhibitor
OT  - mTOR inhibitor associated stomatitis (mIAS)
OT  - stomatitis
OT  - temsirolimus
EDAT- 2015/01/31 06:00
MHDA- 2015/04/18 06:00
CRDT- 2015/01/31 06:00
PHST- 2015/01/31 06:00 [entrez]
PHST- 2015/01/31 06:00 [pubmed]
PHST- 2015/04/18 06:00 [medline]
AID - 10.3109/07357907.2014.1001893 [doi]
PST - ppublish
SO  - Cancer Invest. 2015 Mar;33(3):70-7. doi: 10.3109/07357907.2014.1001893. Epub 2015 
      Jan 30.