title: A Phase I Trial of Temsirolimus and Pemetrexed in Patients with Advanced Non-Small Cell Lung Cancer.
abstract: BACKGROUND
  Pemetrexed is an antifolate chemotherapeutic agent approved for use in non-small cell lung cancer (NSCLC). The mammalian target of rapamycin (mTOR) pathway is implicated in lung cancer development and inhibited by temsirolimus.
  
  
  METHODS
  We performed a phase I study evaluating the combination of pemetrexed and temsirolimus in advanced non-squamous NSCLC.
  
  
  RESULTS
  Eight patients were enrolled in this study. The dose-limiting toxicities included grade 4 thrombocytopenia, grade 3 leukopenia and grade 3 neutropenia. The maximum tolerated dose was determined to be pemetrexed 375 mg/m2 intravenously on day 1 and temsirolimus 25 mg intravenously on days 1, 8 and 15. No objective responses were noted and 3 patients had stable disease as the best response.
  
  
  CONCLUSIONS
  The combination of pemetrexed and temsirolimus is feasible and well tolerated. This combination may be further evaluated in patients with mTOR pathway activation, particularly in those with TSC1 or STK11 mutations.
authors.forename: Saiama N
authors.initials: SN
authors.lastname: Waqar
authors.forename: Maria Q
authors.initials: MQ
authors.lastname: Baggstrom
authors.forename: Daniel
authors.initials: D
authors.lastname: Morgensztern
authors.forename: Kristina
authors.initials: K
authors.lastname: Williams
authors.forename: Caron
authors.initials: C
authors.lastname: Rigden
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Govindan
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009154:Mutation; D000068437:Pemetrexed / Q000008:administration & dosage; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C000624650:TSC1 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; D000068437:Pemetrexed; C401859:temsirolimus; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D058570:TOR Serine-Threonine Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D020123:Sirolimus