title: Hemorrhagic complications in a phase II study of sunitinib in patients of nasopharyngeal carcinoma who has previously received high-dose radiation.
abstract: BACKGROUND
  We aimed to evaluate the safety and efficacy of single-agent sunitinib in nasopharyngeal carcinoma (NPC).
  
  
  METHODS
  Eligible patients had progressive disease after prior platinum-based chemotherapy. Sunitinib was given as continuous once-daily dosing of 37.5 mg in 4-week cycles until progression.
  
  
  RESULTS
  Thirteen patients were enrolled. Recruitment was stopped after two patients died of hemorrhagic events. All patients had previously received curative radiotherapy (RT) to nasopharynx/neck (including nine patients who had chemoradiotherapy). Patients received a median of three cycles of sunitinib. One patient was still on sunitinib with stable disease after 24 cycles. Hemorrhagic events occurred in nine patients (64%), including epistaxis in six, hemoptyses in three and hematemesis in two patients. Prior RT to thorax was significantly associated with hemoptyses (P = 0.03). Two patients with local tumor invasion into the carotid sheath developed fatal epistaxis/hematemesis within the first cycle of sunitinib, likely due to internal carotid blowout after tumor shrinkage.
  
  
  CONCLUSIONS
  Sunitinib demonstrated modest clinical activity in heavily pretreated NPC patients. However, the high incidence of hemorrhage from the upper aerodigestive tract in NPC patients who received prior high-dose RT to the region is of concern. Direct vascular invasion by tumors appeared to increase the risk of serious bleeding.
authors.affiliation: Departments of Clinical Oncology.
authors.forename: E P
authors.initials: EP
authors.lastname: Hui
authors.affiliation: Departments of Clinical Oncology.
authors.forename: B B Y
authors.initials: BBY
authors.lastname: Ma
authors.affiliation: Imaging and Interventional Radiology, Prince of Wales Hospital, Sir YK Pao Center for Cancer, Hong Kong Cancer Institute and Li Ka Shing Institute for Health Sciences, State Key Laboratory in Oncology in South China, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: A D
authors.initials: AD
authors.lastname: King
authors.affiliation: Departments of Clinical Oncology.
authors.forename: F
authors.initials: F
authors.lastname: Mo
authors.affiliation: Departments of Clinical Oncology.
authors.forename: S L
authors.initials: SL
authors.lastname: Chan
authors.affiliation: Departments of Clinical Oncology.
authors.forename: M K M
authors.initials: MKM
authors.lastname: Kam
authors.affiliation: Departments of Clinical Oncology.
authors.forename: H H
authors.initials: HH
authors.lastname: Loong
authors.affiliation: Imaging and Interventional Radiology, Prince of Wales Hospital, Sir YK Pao Center for Cancer, Hong Kong Cancer Institute and Li Ka Shing Institute for Health Sciences, State Key Laboratory in Oncology in South China, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: A T
authors.initials: AT
authors.lastname: Ahuja
authors.affiliation: Departments of Clinical Oncology.
authors.forename: B C Y
authors.initials: BCY
authors.lastname: Zee
authors.affiliation: Departments of Clinical Oncology. Electronic address: anthonytcchan@cuhk.edu.hk.
authors.forename: A T C
authors.initials: ATC
authors.lastname: Chan
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002277:Carcinoma; D059248:Chemoradiotherapy; D004844:Epistaxis / Q000139:chemically induced; D005260:Female; D006396:Hematemesis / Q000139:chemically induced*; D006469:Hemoptysis / Q000139:chemically induced*; D006801:Humans; D007211:Indoles / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000628:therapy*; D011758:Pyrroles / Q000009:adverse effects* / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D040262:Receptors, Vascular Endothelial Growth Factor; D000077210:Sunitinib