Table 1.

Cases of mIAS secondary to everolimus use that describes management strategies

Author (year)	Type of article	Disease	mTOR	Dosage	Intervention	Duration	Discussion
Kalogirou et al13 (2014)	Case series	Renal cell carcinoma and breast cancer	Everolimus	5 mg qd 10 mg qd	Magic Mouthwash* four times daily	3–15 days	mIAS healed in 3–15 days.
Nicolatou-Galitis et al15 (2013)	Case series	HER2+ breast cancer	Everolimus	10 mg qd	Dexamethasone solution 0.5 mg/mL and miconazole 2% gel (1–2 weeks), four patients discontinued everolimus	1–2 weeks	Ulcers healed within 1–2 weeks of either discontinuing everolimus or treatment with dexamethasone solution and miconazole gel
de Oliveira et al6 (2011)	Case series	Cervical chordoma, leiomyosarcoma, osteosarcoma, spindle cell sarcoma, liposarcoma, merkel cell carcinoma, thyroid carcinoma, Waldenstrom macroglobulinaemia	Everolimus Ridaforolimus	10 mg 12.5 mg 40 mg	Topical anaesthetics, Magic Mouthwash†, clobetasol gel 0.05%, dexamethasone 0.1 mg/mL, triamcinolone paste, intralesional triamcinolone, systemic prednisone (1 mg/kg for 7 days)	Variable	Median time to onset of ulcers was 10 days. One of 17 patients discontinued therapy due to mIAS. Five of 17 had dose reductions due to mIAS.
Ferté et al17 (2011)	Chart review	Non-small-cell lung cancer, small-cell lung cancer or breast cancer	Everolimus	Ranged from 2.5 mg qd to 10 mg qd, or 20 mg qw to 30 mg qw	Sodium bicarbonate-based mouthwash, oral fluconazole	Variable	Patients with prior chemotherapy or receiving higher doses of everolimus had higher rates of ulcers and for longer durations. Ten per cent of patients required dose delay because of mIAS and 9% required dose reduction due to mIAS. Empirical treatment with sodium bicarbonate-based mouthwash, oral fluconazole, did not show improvement in mIAS within 5 days after onset.
Sahin et al18 (2011)	Retrospective chart review	Patients who had renal transplant switched from calcineurin-based therapies to sirolimus or everolimus	Sirolimus Everolimus	NA	NA	NA	Reducing calcineurin inhibitor-based therapy, switching to sirolimus or everolimus, was beneficial for GFR
Vermeulen et al19 (2010)	Case report	Severe stomatitis in a patient who had cardiac transplant after switching to everolimus	Everolimus		Local anaesthetic	Not specified	Oral local anaesthetics used but no effect on aphthous ulcers; required discontinuing everolimus secondary to mIAS, requiring conversion to cyclosporine and azathioprine
De Simone et al20 (2009)	Prospective	40 patients who had renal transplants	Everolimus	0.75 mg BID	NA	NA	Everolimus can be used in place of a calcineurin inhibitor-based therapy in patients with liver allograft without a decrease in efficacy.
Ram et al21 (2008)	Case report	Patients who had renal transplant on sirolimus switched to everolimus	Everolimus	0.75 mg BID	Sirolimus switched to everolimus		Patient developed aphthous ulcers on sirolimus and then switched to everolimus. Aphthous ulcers subsequently resolved.
Peterson et al22 (2016)	Literature review	NA	Everolimus Temsirolimus Ridaforolimus Sirolimus	NA	Preventative steroid mouth rinses (NCT02069093)	NA	mIAS can affect the delivery of mTOR inhibitor therapy.
Boers-Doets et al14 (2013)	Literature review	NA	mTOR inhibitors	NA	NA	NA	mIAS are frequent side effects in patients with cancer with genes playing a potential role.

*Magic Mouthwash (lidocaine gel 2%×30 g, doxycycline suspension 50 mg/5 mL×60 mL and sucralfate oral suspension 1000 mg/5 mL dissolved in sodium chloride 0.9%×2000 mL).¹³

^†Magic Mouthwash (lidocaine, aluminium hydroxide, magnesium hydroxide, dimethicone suspension, diphenhydramine, equal parts).

BID, two times a day; GFR, glomerular filtration rate; HER2, human estrogen receptor 2; mIAS, mTOR inhibitor-associated stomatitis; mTOR, mammalian target of rapamycin; qd, four times a day; qw, every week.