Clinical presentation and management of mTOR inhibitor-associated stomatitis

• Published in: Oral oncology Vol. 47; no. 10; pp. 998 - 1003
• Main Authors: de Oliveira, Marcio Augusto, Martins e Martins, Fabiana, Wang, Qian, Sonis, Stephen, Demetri, George, George, Suzanne, Butrynski, James, Treister, Nathaniel S
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.10.2011; Elsevier
• Subjects: Adrenal Cortex Hormones - therapeutic use; Adult; Aged; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Aphthous stomatitis; Biological and medical sciences; Cancer; Everolimus; Facial bones, jaws, teeth, parodontium: diseases, semeiology; Female; Hematology, Oncology and Palliative Medicine; Humans; Male; Mammalian target of rapamycin inhibitor; Medical sciences; Middle Aged; mTOR; Mucositis; Neoplasms - drug therapy; Non tumoral diseases; Otolaryngology; Otorhinolaryngology. Stomatology; Pharmacology. Drug treatments; Retrospective Studies; Sirolimus - adverse effects; Sirolimus - analogs & derivatives; Stomatitis - chemically induced; Stomatitis - drug therapy; TOR Serine-Threonine Kinases - antagonists & inhibitors; Treatment Outcome; Tumors; Aphthous stomatitis; mTOR; Mucositis; Mammalian target of rapamycin inhibitor; Cancer; Antineoplastic agent; Sirolimus; Stomatology; Lactone; ENT; Malignant tumor; Macrolide; Aphta; Macrocycle; Symptomatology; Antibiotic; Stomatitis; Cancerology; Clinical management; mTOR inhibitor; Oral cavity disease; Protein synthesis inhibitor; Immunosuppressive agent; Antibacterial agent
• ISSN: 1368-8375; 1879-0593
• DOI: 10.1016/j.oraloncology.2011.08.009

Summary Anti-cancer agents that inhibit the mTOR pathway are associated with a number of unique toxicities, with one of the most significant and potentially dose-limiting being stomatitis. The objective of this study was to report the clinical features and management outcomes of a series of cancer patients who developed painful mTOR inhibitor-associated stomatitis (mIAS). Seventeen cancer patients developed mIAS while being treated with everolimus- or ridaforolimus-containing protocols at the Dana-Farber Cancer Institute and were referred to the oral medicine clinic for evaluation and management. Clinical characteristics, toxicity management, and outcomes were summarized. In addition, the frequency and rationale for dose reductions and therapy discontinuation were assessed. The median duration of mTOR inhibitor therapy was 80 days (range 9–187 days). The median time to development of mouth ulcers was 10 days (range 4–25 days). Five patients required protocol-directed dose reductions due to grades 2 and 3 stomatitis and one patient discontinued cancer treatment due to mouth ulcers. Clinical improvement and pain relief was reported in 86.6% of patients following topical, intralesional, or systemic corticosteroid therapy, with side effects limited to secondary candidiasis ( n = 2). Mouth ulcers are a common and potentially dose limiting toxicity associated with the use of mTOR inhibitors in cancer treatment. This case series demonstrates that local and systemic corticosteroid therapy is an effective approach to managing patients with symptomatic mIAS. Prospective studies are necessary to evaluate the effectiveness of treatment and prevention strategies with the ultimate goal of improving overall cancer treatment outcomes.