title: Phase II study of sunitinib in patients with non-small cell lung cancer and irradiated brain metastases.
abstract: BACKGROUND
  Brain metastases frequently cause significant morbidity in patients with non-small cell lung cancer (NSCLC). Sunitinib is a multitargeted inhibitor of tyrosine kinase receptors, including vascular endothelial growth factor receptors and platelet-derived growth factor receptors, which has single-agent antitumor activity in refractory NSCLC. This phase II study evaluated the antitumor activity and safety of sunitinib in patients with pretreated NSCLC and irradiated brain metastases.
  
  
  METHODS
  Patients received sunitinib 37.5 mg on a continuous daily dosing schedule. The primary end point was progression-free survival. Secondary end points included overall survival, patient-reported outcomes, and safety, including risk of intracranial hemorrhage (ICH) associated with focal neurological deficit.
  
  
  RESULTS
  Sixty-four patients received sunitinib (median age 61 years), most (83%) had received prior systemic therapy, 63% had adenocarcinoma, and 19% had squamous cell carcinoma; most (55%) were never-smokers. Median progression-free survival was 9.4 weeks (90% confidence interval [CI]: 7.5-13.1), and median overall survival was 25.1 weeks (95% CI: 13.4-35.5). The most common treatment-emergent (all-causality) nonhematologic toxicities (any grade) were fatigue (38%) and decreased appetite and constipation (both 25%). The most common grade 3/4 nonhematologic toxicities were dyspnea (9%) and fatigue (8%). Lymphopenia (20%) and neutropenia (13%) were the most common grade 3/4 hematologic abnormalities. Serious neurologic adverse events occurred in six patients (9%), and none were treatment-related. No cases of ICH were reported.
  
  
  CONCLUSIONS
  Sunitinib administration on a continuous daily dosing schedule in patients with NSCLC and brain metastases was safe and manageable, with no increased risk of ICH.
authors: University of Turin, Orbassano, Turin, Italy. silvia.novello@unito.it
authors: Silvia
authors: S
authors: Novello
authors: Carlos
authors: C
authors: Camps
authors: Francesco
authors: F
authors: Grossi
authors: Julien
authors: J
authors: Mazieres
authors: Lauren
authors: L
authors: Abrey
authors: Jean-Marc
authors: JM
authors: Vernejoux
authors: Aron
authors: A
authors: Thall
authors: Shem
authors: S
authors: Patyna
authors: Tiziana
authors: T
authors: Usari
authors: Zhixiao
authors: Z
authors: Wang
authors: Richard C
authors: RC
authors: Chao
authors: Giorgio
authors: G
authors: Scagliotti