Stomatitis and everolimus: A review of current literature on 8,201 patients

Background: Oral 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 mucocuta-neous eruption, but the most important are still stomatitis and skin rash, which are often dose-limiting side effects. Aim: This review was performed to answer the question “What is the incidence of stomatitis in patients treated with everolimus?” Methods: We 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. Results: The 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). Conclusion: Results 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.