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Ref Type | Journal Article | ||||||||||||
PMID | (24373609) | ||||||||||||
Authors | Waqar SN, Robinson C, Bradley J, Goodgame B, Rooney M, Williams K, Gao F, Govindan R | ||||||||||||
Title | A phase I study of temsirolimus and thoracic radiation in non--small-cell lung cancer. | ||||||||||||
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Abstract Text | 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.This was a phase I study evaluating the combination of temsirolimus with thoracic radiation in patients with NSCLC.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.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. |
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