Phase I trial of erlotinib with radiation therapy in patients with glioblastoma multiforme: results of North Central Cancer Treatment Group protocol N0177

Int J Radiat Oncol Biol Phys. 2006 Jul 15;65(4):1192-9. doi: 10.1016/j.ijrobp.2006.01.018. Epub 2006 Apr 19.


Purpose: To evaluate the toxicity and maximum tolerated dose (MTD) of erlotinib plus radiation therapy (RT) in patients with glioblastoma multiforme (GBM) in a multicenter phase I trial.

Methods and materials: Patients were stratified on the basis of the use of enzyme-inducing anticonvulsants (EIACs). After resection or biopsy, patients were treated with erlotinib for 1 week before concurrent erlotinib and 6 weeks (60 Gy) of RT and maintained on erlotinib until progression. The erlotinib dose was escalated in cohorts of 3 starting at 100 mg/day.

Results: Twenty patients were enrolled and 19 were evaluable for the MTD and efficacy endpoints. Of these patients, 14 were males and 5 were females, with a median age of 54 years. Seven had undergone biopsy only, 5 had subtotal resections, and 7 had gross total resections. The highest dose level was 150 mg/day erlotinib for patients not on EIACs (Group 1) and 200 mg/day for patients on EIACs (Group 2). MTD was not reached in either group. In Group 1 at 100 mg (n=6) and at 150 mg (n=4), only 1 dose-limiting toxicity (DLT) occurred (stomatitis at 100 mg). No DLTs have occurred in Group 2 at 100 mg (n=3), 150 mg (n=3), and 200 mg (n=3). With a median follow-up of 52 weeks, progression was documented in 16 patients and 13 deaths occurred. Median time to progression was 26 weeks, and median survival was 55 weeks.

Conclusion: Toxicity is acceptable at the current doses of erlotinib plus RT. The study was modified to include concurrent and adjuvant temozolomide, and accrual is in progress.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / radiotherapy*
  • Combined Modality Therapy
  • ErbB Receptors / antagonists & inhibitors*
  • Erlotinib Hydrochloride
  • Female
  • Glioblastoma / drug therapy*
  • Glioblastoma / mortality
  • Glioblastoma / radiotherapy*
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Quinazolines / adverse effects
  • Quinazolines / therapeutic use*
  • Radiotherapy Dosage


  • Quinazolines
  • Erlotinib Hydrochloride
  • ErbB Receptors