Phase 1 trial of everolimus and gefitinib in patients with advanced nonsmall-cell lung cancer

Daniel T. Milton, Gregory J. Riely, Christopher G. Azzoli, Jorge E. Gomez, Robert T. Heelan, Mark G. Kris, Lee M. Krug, William Pao, Barbara Pizzo, Naiyer A. Rizvi, Vincent A. Miller

Research output: Contribution to journalArticlepeer-review

94 Scopus citations


BACKGROUND. Preclinical studies have demonstrated that the inhibition of the PI3K/Akt/mTOR pathway restores gefitinib sensitivity in resistant cancer cell lines. A phase 1 study was conducted of the combination of everolimus, an mTOR inhibitor, and gefitinib to determine a daily dose of everolimus with gefitinib in patients with advanced nonsmall-cell lung cancer (NSCLC). METHODS. Oral everolimus and gefitinib were both administered daily to patients with progressive NSCLC. Patients were enrolled in 3-patient cohorts at everolimus dose levels of 5 and 10 mg daily. All patients received gefitinib 250 mg daily. RESULTS. Ten patients were enrolled. The maximum tolerated dose of everolimus was 5 mg when administered daily with gefitinib 250 mg. Two patients who were treated at the 10 mg dose level of everolimus experienced dose-limiting toxicity, including grade 5 hypotension and grade 3 stomatitis. Pharmacokinetic studies demonstrated no consistent, significant interaction on the t max, Cmax, and AUC0-8h of either agent. Two partial radiographic responses were identified among the 8 response-evaluable patients. CONCLUSIONS. For further study, everolimus at a dose of 5 mg daily in combination with daily gefitinib 250 mg is recommended. The 2 radiographic responses identified are encouraging. A phase 2 trial in patients with NSCLC is under way.

Original languageEnglish
Pages (from-to)599-605
Number of pages7
Issue number3
StatePublished - 1 Aug 2007
Externally publishedYes


  • EGFR
  • Everolimus
  • Gefitinib
  • RAD001
  • mTOR


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