title: A phase I trial of sunitinib and rapamycin in patients with advanced non-small cell lung cancer.
abstract: BACKGROUND
  Sunitinib is an oral multitargeted tyrosine kinase inhibitor, with single-agent activity in non-small cell lung cancer (NSCLC). Resistance to tyrosine kinase inhibitor therapy is mediated by the mammalian target of rapamycin (mTOR) pathway, and may be reversed by using mTOR inhibitors.
  
  
  METHODS
  We performed a phase I study evaluating the combination of sunitinib and rapamycin in patients with advanced NSCLC.
  
  
  RESULTS
  Nineteen patients were enrolled in the study. The dose-limiting toxicities included infection, pneumonia, diarrhea/dehydration and treatment delay due to thrombocytopenia in 1 patient each. Sunitinib 25 mg orally daily and rapamycin 2 mg orally daily with 4 weeks on and 2 weeks off therapy were determined to be the maximum tolerated dose. No objective responses were noted, and 6 patients had stable disease as a best response.
  
  
  CONCLUSIONS
  The combination of sunitinib and rapamycin is well-tolerated and warrants further investigation in the phase II setting.
authors: Division of Medical Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors: Saiama N
authors: SN
authors: Waqar
authors: Priya K
authors: PK
authors: Gopalan
authors: Kristina
authors: K
authors: Williams
authors: Siddhartha
authors: S
authors: Devarakonda
authors: Ramaswamy
authors: R
authors: Govindan
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D003967:Diarrhea / Q000209:etiology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib; D020123:Sirolimus