Clinical Study

Journal of Neuro-Oncology

, Volume 110, Issue 2, pp 245-250

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

A dose escalation trial for the combination of erlotinib and sirolimus for recurrent malignant gliomas

  • Phioanh Leia NghiemphuAffiliated withDepartment of Neurology, University of California Email author 
  • , Albert LaiAffiliated withDepartment of Neurology, University of California
  • , Richard M. GreenAffiliated withDepartment of Neurology, Kaiser Permanente
  • , David A. ReardonAffiliated withCenter for Neuro-Oncology, Dana-Farber Cancer Institute
  • , Timothy CloughesyAffiliated withDepartment of Neurology, University of California


In order to achieve higher dosages than previously used in clinical trials, we conducted a phase I trial to determine the maximum tolerated dose (MTD) for the combination of erlotinib and sirolimus for the treatments of recurrent malignant gliomas. Patients with pathologically proven World Health Organization (WHO) grade III glioma and grade IV glioblastoma and radiographically proven tumor recurrence were eligible for this study. Treatments included once daily erlotinib, which was given alone for the first 7 days of treatments, then in combination with once daily sirolimus. Sirolimus was given with a loading dose on day 8 followed by a maintenance dose starting on day 9. Dose-limiting toxicity (DLT) was determined over the first 28 days of treatments, and the MTD was determined in a 3 + 3 classic study design. 19 patients were enrolled, and 13 patients were eligible for MTD determination. The MTD was determined to be 150 mg daily for erlotinib and 5 mg daily (after a 15 mg loading dose) for sirolimus. The DLTs included rash and mucositis (despite maximal medical managements), hypophosphatemia, altered mental status, and neutropenia. The combination of erlotinib and sirolimus is difficult to tolerate at dosages higher than previously reported in phase II trials.


Erlotinib Sirolimus Recurrent gliomas Combination study