Laryngeal Side Effects of Tyrosine Kinase Inhibitors.
OBJECTIVE
Tyrosine kinase inhibitors (TKIs) are common targeted drugs, used in the treatment of hematological and solid malignancies. These drugs present a multitude of potential adverse effects. Laryngeal manifestations, including laryngeal edema, secondary to TKIs treatment have not been well studied, despite their potential lethality.


METHODS
This cross-sectional study included adult patients (>18 years) treated with TKIs who were followed in a secondary medical center and underwent a voluntary otolaryngological examination, which included laryngeal fiber-optic laryngoscopy (FOL). FOL was independently performed by two senior otolaryngologists, and results were recorded and evaluated by two grading systems, to assess the degree of laryngeal edema. In addition, medical files were reviewed, and data collected included past medical history, signs and symptoms, physical examination, laboratory results, treatment type, and duration.


RESULTS
Sixteen patients, aged 68.2 ± 13.6 years, were examined during October 2014 to December 2014. Of them, three (19%) were males. Eleven (68%) patients presented with varying degrees of laryngeal edema. A significant correlation was found between gastroesophageal reflux symptoms and laryngeal edema (P = 0.02). TKI treatment was stopped in one patient, because of symptomatic laryngeal edema, which completely resolved within 2 weeks.


CONCLUSIONS
Laryngeal edema was common in our study group. This edema was most often not life threatening. Yet, because of the potential severity of this side effect, we propose a routine FOL examination of patients before commencing TKI treatment and a reevaluation performed during treatment.
Department of Otolaryngology-Head and Neck Surgery, Edith Wolfson Medical Center, Tel Aviv University Sackler School of Medicine, Holon, Israel. Electronic address: sharontamir@gmail.com.
Sharon
S
Ovnat Tamir
Department of Otolaryngology-Head and Neck Surgery, Edith Wolfson Medical Center, Tel Aviv University Sackler School of Medicine, Holon, Israel.
Dafna
D
Gershnabel Milk
Department of Otolaryngology-Head and Neck Surgery, Edith Wolfson Medical Center, Tel Aviv University Sackler School of Medicine, Holon, Israel.
Yehudah
Y
Roth
Department of Otolaryngology-Head and Neck Surgery, Edith Wolfson Medical Center, Tel Aviv University Sackler School of Medicine, Holon, Israel.
Udi
U
Cinamon
Hematology Unit, Edith Wolfson Medical Center, Tel Aviv University Sackler School of Medicine, Holon, Israel.
Asher
A
Winder
Oncology Unit, Edith Wolfson Medical Center, Tel Aviv University Sackler School of Medicine, Holon, Israel.
Ronen
R
Brenner
Department of Otolaryngology-Head and Neck Surgery, Edith Wolfson Medical Center, Tel Aviv University Sackler School of Medicine, Holon, Israel.
Ariel
A
Katz
Department of Otolaryngology-Head and Neck Surgery, Edith Wolfson Medical Center, Tel Aviv University Sackler School of Medicine, Holon, Israel.
Tal
T
Marom
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003430:Cross-Sectional Studies; D004417:Dyspnea / Q000139:chemically induced; D005260:Female; D005764:Gastroesophageal Reflux / Q000150:complications; D006685:Hoarseness / Q000139:chemically induced; D006801:Humans; D007819:Laryngeal Edema / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D007828:Laryngoscopy; D007830:Larynx / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000009:adverse effects*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012307:Risk Factors; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects; D011795:Surveys and Questionnaires; D014831:Voice / Q000187:drug effects
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases
Edema; Fiber-optic laryngoscopy; Larynx; Tyrosine kinase inhibitor