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Review
. 2012;17(1):135-44.
doi: 10.1634/theoncologist.2011-0111. Epub 2011 Dec 29.

Oral adverse events associated with tyrosine kinase and mammalian target of rapamycin inhibitors in renal cell carcinoma: a structured literature review

Christine B Boers-Doets  1 , Joel B Epstein, Judith E Raber-Durlacher, Jan Ouwerkerk, Richard M Logan, Jan A Brakenhoff, Mario E Lacouture, Hans Gelderblom
Affiliations
Review

Oral adverse events associated with tyrosine kinase and mammalian target of rapamycin inhibitors in renal cell carcinoma: a structured literature review

Christine B Boers-Doets et al. Oncologist. 2012.

Abstract

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.

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Conflict of interest statement

Disclosures

Christine B. Boers-Doets: Bayer Pharmaceuticals, Novartis, Pfizer, Wyeth, GlaxoSmithKline, Amgen, Roche, EUSA Pharma, Merck Sharp and Dohme, MerckSerono (C/A, H); Joel B. Epstein: None; Judith E. Raber-Durlacher: EUSA Pharma (C/A, H); Jan Ouwerkerk: Pfizer, GlaxoSmithKline, Amgen, Roche, MerckSerono (C/A, H); Richard M. Logan: None; Jan A. Brakenhoff: None; Mario E. Lacouture: Amgen, Bayer Pharmaceuticals, Bristol-Myers Squibb, Exelixis, Genentech, Hana Biosciences (now Talon Therapeutics), GlaxoSmithKline, ImClone, Lindi Skin, Onyx Pharmaceuticals, OSI Pharmaceuticals Inc., Pfizer, Roche, Sanofi-Aventis (C/A, H); Hans Gelderblom: Novartis (RF).

Section Editors Eduardo Bruera: None; Russell K. Portenoy: Arsenal Medical Inc., Grupo Ferrer, Xenon (C/A); Ameritox, Archimedes Pharmaceuticals, Boston Scientific, Covidien Mallinckrodt Inc., Endo Pharmaceuticals, Forest Labs, K-Pax Pharmaceuticals, Meda Pharmaceuticals, Medtronics, Otsuka Pharma, ProStrakan, Purdue Pharma, Salix, St. Jude Medical (RF).

Reviewer “A”: Biomodels, LLC (partner), Novartis, Pfizer, Merck, Clinical Assistance Programs, Actogenix (C/A).

Reviewer “B”: Acacia Pharma (C/A); Roche, Amgen, Novartis, EUSA Pharma, Merck Serono (H).

Figures

Figure 1.
Figure 1.
Mammalian target of rapamycin inhibitor (mTORI)-induced hand–foot skin reaction (HFSR). HFSR caused by temsirolimus, an mTORI. HFSR is associated with symptoms that are seen with oral adverse events too. As shown in this picture, patients can develop localized, tender lesions that appear as blisters or hyperkeratosis, which in some cases can be surrounded by an erythematous halo.
Figure 2.
Figure 2.
Mammalian target of rapamycin inhibitor (mTORI)-induced oral adverse events. Aphthous stomatitis caused by temsirolimus, an mTORI. As shown in this picture, patients can develop localized, tender lesions that appear as aphthous stomatitis and that can be surrounded by an erythematous halo.
See this image and copyright information in PMC

References

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