title: A phase I study of temsirolimus and thoracic radiation in non--small-cell lung cancer.
abstract: BACKGROUND
  The addition of targeted agents to thoracic radiation has not improved outcomes in patients with locally advanced non-small-cell lung cancer (NSCLC). To improve cure rates in locally advanced NSCLC, effective targeted therapies need to be identified that can be given safely with radiation therapy. Temsirolimus is an inhibitor of the mammalian target of rapamycin (mTOR) pathway and has single-agent activity in lung cancer. Inhibition of the mTOR pathway has been found to augment the cytotoxic effect of radiation in preclinical studies. There is scant clinical experience with mTOR inhibitors and radiation.
  
  
  METHODS
  This was a phase I study evaluating the combination of temsirolimus with thoracic radiation in patients with NSCLC.
  
  
  RESULTS
  Ten patients were enrolled in the study. The dose-limiting toxicities included sudden death, pneumonitis, and pulmonary hemorrhage. The maximum tolerated dose of temsirolimus that could be administered safely with concurrent radiotherapy (35 Gy in 14 daily fractions) was 15 mg intravenously weekly. Of the 8 evaluable patients, 3 had a partial response and 2 had stable disease.
  
  
  CONCLUSIONS
  The combination of temsirolimus 15 mg weekly and thoracic radiation is well tolerated and warrants further investigation, perhaps in a molecularly defined subset of patients.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO.
authors.forename: Saiama N
authors.initials: SN
authors.lastname: Waqar
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO.
authors.forename: Clifford
authors.initials: C
authors.lastname: Robinson
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bradley
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Boone
authors.initials: B
authors.lastname: Goodgame
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO.
authors.forename: Melissa
authors.initials: M
authors.lastname: Rooney
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO.
authors.forename: Kristina
authors.initials: K
authors.lastname: Williams
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St Louis, MO.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO. Electronic address: rgovinda@dom.wustl.edu.
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Govindan
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011879:Radiotherapy Dosage; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; C401859:temsirolimus; D020123:Sirolimus
keywords: Non–small-cell lung cancer; Radiation; Temsirolimus