Hemorrhagic complications in a phase II study of sunitinib in patients of nasopharyngeal carcinoma who has previously received high-dose radiation

Ann Oncol. 2011 Jun;22(6):1280-1287. doi: 10.1093/annonc/mdq629. Epub 2011 Feb 11.

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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Carcinoma
  • Chemoradiotherapy
  • Epistaxis / chemically induced
  • Female
  • Hematemesis / chemically induced*
  • Hemoptysis / chemically induced*
  • Humans
  • Indoles / adverse effects*
  • Indoles / therapeutic use
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / therapy*
  • Pyrroles / adverse effects*
  • Pyrroles / therapeutic use
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
  • Sunitinib
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Indoles
  • Pyrroles
  • Receptors, Vascular Endothelial Growth Factor
  • Sunitinib