Oral stomatitis and <scp>mTOR</scp> inhibitors: A review of current evidence in 20,915 patients

Muzio, Lorenzo Lo; Arena, Claudia; Troiano, Giuseppe; Villa, Alessandro

doi:10.1111/odi.12795

Cited by 23 publications

(15 citation statements)

References 152 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Unlike results obtained from reviews about mucositis caused by conventional chemotherapy, in which mucositis is often severe and the most debilitating effect for patients,18 our analysis showed that the incidence of stomatitis of grade 1 or 2 is higher than that of grade 3 or 4. These results are consistent with our previous work 19. However, it must be taken into account that it is not possible to say if side effects are entirely due to everolimus therapy or combination with other drugs.…”

Section: Discussionsupporting

confidence: 92%

<p>Stomatitis And Everolimus: A Review Of Current Literature On 8,201 Patients</p>

Arena¹,

Troiano²,

Zhurakivska³

et al. 2019

OTT

Self Cite

View full text Add to dashboard Cite

BackgroundOral toxicities, such as mucositis and stomatitis, are some of the most significant and unavoidable side effects associated with anticancer therapies. In past decades, research has focused on newer targeted agents with the aim of decreasing the rates of side effects on healthy cells. Unfortunately, even targeted anticancer therapies show significant rates of toxicity on healthy tissue. mTOR inhibitors display some adverse events, such as hyperglycemia, hyperlipidemia, hypophosphatemia, hematologic toxicities, and mucocutaneous eruption, but the most important are still stomatitis and skin rash, which are often dose-limiting side effects.AimThis review was performed to answer the question “What is the incidence of stomatitis in patients treated with everolimus?”MethodsWe conducted a systematic search on the PubMed and Medline online databases using a combination of MESH terms and free text: “everolimus” (MESH) AND “side effects” OR “toxicities” OR “adverse events”. Only studies fulfilling the following inclusion criteria were considered eligible for inclusion in this study: performed on human subjects, reporting on the use of everolimus (even if in combination with other drugs or ionizing radiation), written in the English language, and reporting the incidence of side effects.ResultsThe analysis of literature revealed that the overall incidence of stomatitis after treatment with everolimus was 42.6% (3,493) and that of stomatitis grade G1/2 84.02% (2,935), while G3/4 was 15.97% (558).ConclusionResults of the analysis showed that the incidence of stomatitis of grade 1 or 2 is higher than grade 3 or 4. However, it must be taken into account that it is not possible to say if side effects are entirely due to everolimus therapy or combinations with other drugs.

show abstract

Section: Discussionsupporting

confidence: 92%

<p>Stomatitis And Everolimus: A Review Of Current Literature On 8,201 Patients</p>

Arena¹,

Troiano²,

Zhurakivska³

et al. 2019

OTT

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, other classes of targeted anti-cancer therapies with immunologic activities as mTOR inhibitors are known to induce stomatitis. In a review, Lo Muzio et al showed that the incidence rate of stomatitis based on the agent used was 54.76% for ridaforolimus, 27.02% for temsirolimus, and 25.07% for everolimus even if the onset of severe stomatitis (G3-G4) was uncommon [114]. Concerning a way to improve the adherence (acceptability) of patients to the chemopreventive protocol treatment, a recent study by Samimi et al indicated that patients could be more receptive to locally delivered chemopreventive compounds if they believe these substances useful for the treatment of cancer [115].…”

Section: Discussionmentioning

confidence: 99%

Leukoplakia and Immunology: New Chemoprevention Landscapes?

Grigolato

Bizzoca

Calabrese

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Oral potentially malignant disorders (OPMDs) comprise a range of clinical-pathological alterations frequently characterized by an architectural and cytological derangements upon histological analysis. Among them, oral leukoplakia is the most common type of these disorders. This work aims to analyze the possible use of drugs such as immunochemopreventive agents for OPMDs. Chemoprevention is the use of synthetic or natural compounds for the reversal, suppression, or prevention of a premalignant lesion conversion to malignant form. Experimental and in vivo data offer us the promise of molecular prevention through immunomodulation; however, currently, there is no evidence for the efficacy of these drugs in the chemoprevention action. Alternative ways to deliver drugs, combined use of molecules with complementary antitumor activities, diet influence, and better definition of individual risk factors must also be considered to reduce toxicity, improve compliance to the protocol treatment and offer a better individualized prevention. In addition, we must carefully reconsider the mode of action of many traditional cancer chemoprevention agents on the immune system, such as enhancing immunosurveillance and reversing the immune evasion. Several studies emphasize the concept of green chemoprevention as an alternative approach to accent healthy lifestyle changes in order to decrease the incidence of HNSCC.

show abstract

“…In a recent retrospective study, Krueger also reported that 40% of children developed stomatitis during mTOR inhibitor treatment [31]. According to the reviews by Martins [32] and Lo Muzio [33], grade 1 and grade 2 stomatitis occur more frequently in the first treatment cycle and seem to depend on the dose. Theoretically, mTOR inhibitors may induce an inflammatory reaction by inducing the release of keratinocyte cytokines, directly causing epithelial injury, which results in stomatitis [34].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of mTOR inhibitors (rapamycin and its analogues) for tuberous sclerosis complex: a meta-analysis

Zhou

Chen

et al. 2019

Orphanet J Rare Dis

View full text Add to dashboard Cite

BackgroundThe treatment of tuberous sclerosis complex (TSC) using mammalian target of rapamycin (mTOR) inhibitors is clinically promising. The aim of the present study was to evaluate the efficacy and safety of mTOR inhibitors for improving the clinical symptoms of TSC.MethodsWe performed a systematic search of major electronic databases (PubMed, EMBASE, Cochrane Library and WanFang, CNKI, and VIP databases) to identify randomized controlled trials (RCTs) and quasi-randomized studies from the date of database inception to November 2017; the Chinese Food and Drug Administration and clinicaltrials.gov were also searched for unpublished studies. The endpoints of the study were the tumor response rate and seizure frequency response rate (the proportion of patients achieving a ≥ 50% reduction relative to the baseline). Two researchers screened articles, assessed the risk of bias and extracted data independently. The included RCTs were analyzed using RevMan 5.3, which was provided by the Cochrane Collaboration.ResultsCompared with the placebo, mTOR inhibitors significantly reduced tumor volume in both angiomyolipoma (AML) (RR = 24.69, 95% CI = 3.51,173.41, P = 0.001) and subependymal giant cell astrocytoma (SEGA) (RR = 27.85, 95% CI = 1.74,444.82, P = 0.02). Compared with the placebo, mTOR inhibitors significantly reduced seizure frequency (RR = 2.12, 95% CI = 1.41,3.19, P = 0.0003). Regarding safety, compared with patients who did not receive mTOR inhibitors, those who did had a higher risk of suffering stomatitis (RR = 3.20, 95% CI = 1.49,6.86, P = 0.003). In contrast, patients who did and did not receive mTOR inhibitors experienced similar adverse events, such as upper respiratory tract infections (RR = 1.08, 95% CI = 0.81,1.45, P = 0.59) and nasopharyngitis (RR = 0.86, 95% CI = 0.60,1.21, P = 0.38).ConclusionIn view of the efficacy and safety associated with tumor and seizure frequency in the TSC patients, mTOR inhibitors is a good therapeutic choice. Unlike the risks of upper respiratory tract infections and nasopharyngitis, mTOR inhibitors seem to increase the risk of stomatitis, mostly grade 1 and 2.

show abstract

Oral stomatitis and mTOR inhibitors: A review of current evidence in 20,915 patients

Abstract: Analysis of the reports with patients treated with everolimus, temsirolimus, and ridaforolimus showed a clear prevalence of stomatitis grade 1 or 2. These data differ from that of patients treated with conventional chemotherapy in which mucositis is predominantly of grade 3 or 4.

Cited by 23 publications

References 152 publications

<p>Stomatitis And Everolimus: A Review Of Current Literature On 8,201 Patients</p>

<p>Stomatitis And Everolimus: A Review Of Current Literature On 8,201 Patients</p>

Leukoplakia and Immunology: New Chemoprevention Landscapes?

Efficacy and safety of mTOR inhibitors (rapamycin and its analogues) for tuberous sclerosis complex: a meta-analysis

Contact Info

Product

Resources

About