1502 Purpose: To evaluate the efficacy of OSI-774, a small molecule tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), in patients with recurrent malignant gliomas not on enzyme induce anti-convulsant drugs (EIAEDs).
METHODS
Pts with recurrent MG were treated with OSI-774 at a dose of 150 mg/day continuously. Patients could not have had more than 2 prior chemotherapies. Patients were evaluated for response with MRI every 56 days. PK studies and AGP levels were done in most patients.
RESULTS
67 pts enrolled onto this arm of the study but only the 45 pts with recurrent MG are reported here.
HISTOLOGY
30 (20M/10F) pts had glioblastoma multiformes (GBMs) and 15 (7M/8F) pts had anaplastic gliomas (AGs). Median age and KPS was 58 years and 80 for GBMs and 43 years and 90 for AGs. The median PFS for GBM was 12 wks (95% CI; 7.6 to 13 weeks) with no GBM pts progression free at 24 weeks; best response was SD in 4 pts. For AGs median PFS was 8.6 wks (CI; 3.7 to 45 wks) with 4 patients still on study; best response was 1 PR (unconfirmed) and 2 SD. Cycle 1 toxicities: Gr 3-Rash and hypokalemia all others were Gr 1 and 2, primarily rash, diarrhea, fatigue, and bilirubin elevation. PK studies on 20 pts, found an AUC0-24 for OSI-774 was 13.1 ugxh/ml and for OSI-420 875 ngxh/ml; the Cpmax (ng/ml) was 895 and 64 for OSI-774 and OSI-420.
CONCLUSION
We completed a phase II trial of OSI-774 in patients with MGs not on EIAEDs. While a few patients had SD and 1 had a PR the median PFS and the 24 week PFS suggest that for GBMs and AGs that OSI-774 has limited activity as a single agent. Toxicities were primarily Gr 1 and 2 and tolerable. [Table: see text].