title: Oral adverse events in cancer patients treated with VEGFR-directed multitargeted tyrosine kinase inhibitors.
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Anna
authors.initials: A
authors.lastname: Yuan
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: Sharyn L
authors.initials: SL
authors.lastname: Kurtz
authors.affiliation: Department of Biostatistics and Computational Biology, 450 Brookline Avenue, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
authors.forename: Constance M
authors.initials: CM
authors.lastname: Barysauskas
authors.affiliation: Department of Medical Oncology, Rhode Island Hospital Comprehensive Cancer Center, 1454 South County Trail, Suite 2100, East Greenwich, RI 02818, USA.
authors.forename: Amy P
authors.initials: AP
authors.lastname: Pilotte
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wagner
authors.affiliation: 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.
authors.forename: Nathaniel S
authors.initials: NS
authors.lastname: Treister
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009059:Mouth Diseases / Q000139:chemically induced*; D009369:Neoplasms / Q000188:drug therapy*; D010292:Paresthesia / Q000139:chemically induced; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Mucositis; Oral adverse events; Oral complications; Oral dysesthesia; Oral toxicities; Stomatitis; Sunitinib; Sutent; Targeted cancer therapy; Tyrosine kinase inhibitors