Oral medicine
Online only article
Oral ulcers in patients with advanced breast cancer receiving everolimus: a case series report on clinical presentation and management

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Objective

We report the clinical features and management outcomes in 7 patients with everolimus-related stomatitis.

Study design

Fifteen women with hormone-receptor-positive advanced breast cancer receiving everolimus combined with exemestane were prospectively evaluated to assess the development of stomatitis. Oral ulcers were diagnosed based on established criteria.

Results

Seven patients developed stomatitis (46.6%). All patients were treated with topical dexamethasone solution, while everolimus was temporarily discontinued in 4 patients. Stomatitis resolved within 1-2 weeks. Two of the 4 patients, who had interrupted everolimus, developed recurrent stomatitis following drug resume and everolimus was again discontinued and restarted after 2 weeks. To date, 5 patients receive everolimus in full dose. The 2 patients, who developed recurrent stomatitis, received a reduced dose.

Conclusions

Everolimus-related oral ulcers were frequent and led to dose modifications. Controlled trials, endorsing a consensus in terminology, are needed to evaluate measures on prevention and management of this unique toxicity.

Section snippets

Patients

Seven of 15 women with hormone-receptor-positive, recurrent or progressive advanced breast carcinoma, treated with everolimus (10 mg daily) combined with exemestane (25 mg daily), who developed stomatitis were prospectively evaluated from April 2012 to September 2012. Written informed consent was obtained from all patients.

Methods

Patients reporting the occurrence of oral pain during the course of antitumor therapy were referred to trained assessors for oral assessment. Oral lesions were recorded in

Results

All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 and adequate organ and hematologic functions.22 All patients had metastatic disease, mainly visceral and/or bone, and had received prior treatment for their primary tumor. Seven of 15 patients (46.7%) complained of oral pain and were consequently diagnosed with mTORI stomatitis. The characteristics of the 2 groups, group 1 (patients without stomatitis) and group 2 (patients with stomatitis), are shown in

Discussion

In this report we prospectively assessed the clinical features, management, course and clinical outcome of oral ulcers in a series of 7 of 15 women (46.6%) with advanced breast cancer who received everolimus combined with exemestane.

The 46.6% prevalence of stomatitis, all grades, was within the range reported previously, in clinical trials, in patients receiving different mTORIs.8, 9, 10, 11, 12, 13, 15, 16, 23, 24, 25 Oral ulcer prevalence was closer to that reported when everolimus was

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  • Cited by (23)

    • Prevention of everolimus-related stomatitis in women with hormone receptor-positive, HER2-negative metastatic breast cancer using dexamethasone mouthwash (SWISH): a single-arm, phase 2 trial

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      Management of mTOR inhibitor-associated stomatitis by dose delays, reductions, or discontinuation of the mTOR inhibitor might compromise duration and intensity of therapy and might affect decisions to initiate treatment with mTOR inhibitors.3 Aphthous ulcers have been treated successfully by steroid-containing oral paste or rinse; anecdotal reports suggested that topical steroids could improve healing of everolimus-associated aphthous ulcers.3,8,10 Until now, clinical evidence has been scarce to guide mTOR inhibitor-associated stomatitis prophylactic strategies.

    • MTOR inhibitor-associated stomatitis (mIAS) in three patients with cancer treated with everolimus

      2015, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
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      As in a previous report,1 all cases presented here were considered to be grade 2, although one of the patients had been pretreated with sunitinib malate, and the other two were using exemestane concurrently. Previous chemotherapy and concurrent use of other antineoplastic agents or exemestane may have no effect1,9 or increase3 the incidence of mIAS, but a combination of mTORI with other antineoplastic drugs is usually associated with more severe symptoms.3,9 No other oral adverse events of mTORI, that is, xerostomia, taste alteration, or gingival swelling, and gastrointestinal or skin involvement,5,6,8 were reported by our patients.

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      Although specific strategies to prevent or manage (or both) everolimus-associated stomatitis are not well documented, the use of specific oral steroid rinses (eg, dexamethasone solution) and steroid-based mouthwashes (eg, “miracle mouthwash” or “magic mouthwash” formulations) has been suggested for preventing and treating mTOR inhibitor–associated stomatitis (Table 2).52-54 Previous reports have suggested that stomatitis can be mitigated with the use of a 5% dexamethasone oral rinse.50,55 Additionally, the use of a steroid mouth rinse is currently being evaluated to treat stomatitis as a secondary end point in the BOLERO-4 study as well as to prevent stomatitis in a phase II trial of everolimus plus exemestane in HR+/HER− advanced BC (ClinicalTrials.gov identifier: NCT02069093).

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