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Medline ® Abstract for Reference 168

of 'Toxicity of molecularly targeted antiangiogenic agents: Non-cardiovascular effects'

Oral adverse events in cancer patients treated with VEGFR-directed multitargeted tyrosine kinase inhibitors.
Yuan A, Kurtz SL, Barysauskas CM, Pilotte AP, Wagner AJ, Treister NS
Oral Oncol. 2015;51(11):1026. Epub 2015 Oct 5.
OBJECTIVES: This study characterized the incidence and clinical features of oral adverse events among cancer patients who received VEGFR-directed multitargeted tyrosine kinase inhibitor (VR-TKI) therapies.
METHODS: Electronic medical records of adult cancer patients treated with sunitinib, sorafenib, regorafenib, pazopanib, cabozantinib, imatinib, and bevacizumab therapy at Dana-Farber Cancer Institute from 2009 to 2012 were reviewed. Data collected included patient characteristics, oral and non-oral adverse events, and time to onset. Time oral adverse event-free was the primary outcome.
RESULTS: A total of 747 patients with 806 individual courses of therapy were treated for a median of 3.9months with sunitinib (n=161), sorafenib (n=172), regorafenib (n=15), pazopanib (n=132), cabozantinib (n=23), imatinib (n=144), or bevacizumab (n=159) for lung cancer (21%), gastrointestinal stromal tumor (15%), and metastatic renal cell carcinoma (13%). An oral adverse event was reported in 23.7% of patients at a median of 1.9months after starting therapy. The most commonly reported oral adverse event was oral mucosal sensitivity (dysesthesia), occurring in 12% of patients, typically without clinical findings. Multivariate models showed patients who received VR-TKI therapy were at greater risk of any oral adverse event compared with patients treated with imatinib or bevacizumab. Patients receiving VR-TKI therapy who developed an oral adverse event were also at increased risk for hand-foot skin reaction (15.9%).
CONCLUSIONS: VR-TKI associated oral adverse events are characterized primarily by dysesthesia with lack of clinical signs. Oral dysesthesia is more commonly associated with VR-TKIs than with bevacizumab or imatinib. Management is largely empirical and requires further investigation.
Division of Oral Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA; Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA. Electronic address: annayuan@post.harvard.edu.