An update of phase I data from RTOG 0211: A phase I/II clinical study of gefitinib+ radiation for newly-diagnosed glioblastoma (GBM) patients

Abstract

1571 Background: The Radiation Therapy Oncology Group (RTOG) initiated a Phase I/II clinical study of the EGFR tyrosine kinase inhibitor, Gefitinib, in combination with radiation for newly diagnosed GBM patients. This report is an update of Phase I toxicity data. Methods: Patients entered on RTOG 0211 were stratified into two groups based on whether they were on enzyme-inducing anticonvulsant drugs (EIACDs:Group I) or not (non-EIACDs: Group II). The planned Gefitinib dose escalation during radiation was from 250 to 750mg in Group I and 250 to 500mg in Group II in 250 mg increments. A standard 3+3 design was used to evaluate dose-limiting toxicities (DLTs), which were defined as designated acute (<90 days) toxicity events. Results: A total of 18 patients in Group I (16 eligible and analyzable) and 13 patients in Group II (12 eligible and analyzable) were included in this update. In Group I, no DLTs were observed up to 750 mg. One subject in Group I had late (>90 days) Grade 3 elevation of SGOT. In Group II, one subject experienced a Grade 3 elevation of SGOT at the 250 mg dose level within 90 days. At the 500 mg dose level in Group II, one patient had late Grade 3 elevation of SGOT and one patient had acute Grade 4 elevation of SGOT. Other observed side-effects (e.g. fatigue, skin rash, headaches, seizures) did not fit the definition of DLTs or were deemed to be unrelated to Iressa. Conclusions: Gefitinib in combination with radiation appears to be well-tolerated in GBM patients at the dose levels examined. Further dose escalation is being planned for Group I, given the favorable side-effect profile in EIACD patients in this, as well as previously reported studies in the setting of recurrent disease. For non-EIACD patients, the Phase II component of the study has been initiated at the 500 mg dose level. No significant financial relationships to disclose.