title: Risk of rash in cancer patients treated with vandetanib: systematic review and meta-analysis.
abstract: BACKGROUND
  Vandetanib is an oral inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection tyrosine kinases. It is approved for the treatment of unresectable or metastatic medullary thyroid cancer. Its use may be hindered due to adverse events, including rash. The reported incidence and risk of rash to vandetanib varies widely and has not been more closely investigated. Therefore, we conducted a systematic review and meta-analysis of the literature to determine the incidence and risk of developing a rash.
  
  
  METHODS
  Databases from PubMed from 1996 through July 2011 and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through July 2011 were searched for relevant studies.
  
  
  METHODS
  Eligible studies were prospective trials that described side effects of all-grade or high-grade rash for patients who received vandetanib 300 mg as a single agent. The incidence of all-grade and high-grade rash and relative risk were calculated using random-effects or fixed-effects models.
  
  
  RESULTS
  Of 63 studies initially identified, nine met the selection criteria and were included for the study. A total of 2961 patients were included for analysis. The summary incidences of all-grade and high-grade rash were 46.1% [95% confidence interval (CI), 40.6-51.8%] and 3.5% (95% CI, 2.5-4.7%), respectively. From randomized controlled trials, patients who received vandetanib 300 mg had a significantly increased risk of developing all-grade rash in comparison with controls, with a relative risk of 2.43 (95% CI, 1.37-4.29; P = 0.002).
  
  
  CONCLUSIONS
  There is a significant risk of developing rash in cancer patients receiving vandetanib. Awareness and treatment of this adverse event is critical to ensure adherence and maximize dosing, guaranteeing the best possible clinical benefit.
authors.affiliation: Dermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Rockefeller Outpatient Pavilion, Suite 228, 160 East 53rd Street, New York, New York 10022, USA.
authors.forename: Alyx C
authors.initials: AC
authors.lastname: Rosen
authors.forename: Shenhong
authors.initials: S
authors.lastname: Wu
authors.forename: Amelia
authors.initials: A
authors.lastname: Damse
authors.forename: Eric
authors.initials: E
authors.lastname: Sherman
authors.forename: Mario E
authors.initials: ME
authors.lastname: Lacouture
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy; D018278:Carcinoma, Neuroendocrine; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003875:Drug Eruptions / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D010880:Piperidines / Q000009:adverse effects* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D051096:Proto-Oncogene Proteins c-ret / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000009:adverse effects* / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D012306:Risk; D012720:Severity of Illness Index; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy; D013964:Thyroid Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D040262:Receptors, Vascular Endothelial Growth Factor; C452423:vandetanib