Oral adverse events associated with tyrosine kinase and mammalian target of rapamycin inhibitors in renal cell carcinoma: a structured literature review.
BACKGROUND
Oral adverse events (OAEs) associated with multitargeted tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors (mTORIs) are underestimated but frequent and novel presentations of mucosal manifestations. Because optimal antitumor activity requires maintaining the optimal dose, it is essential to avoid unintended treatment delays or interruptions.


METHODS
We review the reported prevalence and appearance of OAEs with TKIs and mTORIs and the current oral assessment tools commonly used in clinical trials. We discuss the correlations between OAEs and hand-foot skin reaction (HFSR) and rash.


RESULTS
The reported prevalence of oral mucositis/stomatitis of any grade is 4% for pazopanib, 28% for sorafenib, 38% for sunitinib, 41% for temsirolimus, and 44% for everolimus. Oral lesions associated with these agents have been reported to more closely resemble aphthous stomatitis than OM caused by conventional agents. In addition, these agents may result in symptoms such as oral mucosal pain, dysgeusia, and dysphagia, in the absence of clinical lesions. Because of these factors, OAEs secondary to targeted agents may be underreported. In addition, a correlation between OAEs and HFSR was identified.


CONCLUSIONS
OAEs caused by TKIs and mTORIs may represent dose-limiting toxicities, especially considering the fact that even low grades of OAEs may be troubling to the patient. We discuss how these novel AEs can be assessed because current mucositis assessment tools have limitations. Prospective studies investigating the pathogenesis, risk factors, and management of OAEs are needed in order to minimize the impact on patient's health-related quality of life.
Oncology Clinical Trials Office Waterland Hospital, Oncology Clinical Trials Office, P.O. Box 250, 1440 AG Purmerend, The Netherlands. CBoers@wlz.nl
Christine B
CB
Boers-Doets
Joel B
JB
Epstein
Judith E
JE
Raber-Durlacher
Jan
J
Ouwerkerk
Richard M
RM
Logan
Jan A
JA
Brakenhoff
Mario E
ME
Lacouture
Hans
H
Gelderblom
D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D052016:Mucositis / Q000139:chemically induced; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013280:Stomatitis / Q000139:chemically induced; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; D011505:Protein-Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases