Phase II trial of imatinib mesylate and hydroxyurea for adults with recurrent/progressive low-grade glioma

Abstract

2053 Background: We evaluated the combination of imatinib mesylate and hydroxyurea in recurrent/progressive low-grade gliomas (LGG) following the encouraging response of this combination demonstrated among adults with recurrent malignant glioma. Methods: Key eligibility criteria: age over 18 yrs; histologically confirmed grade II LGG that is recurrent/progressive following at least prior surgical resection; Karnofsky = 60% and adequate organ function. Imatinib plus hydroxyurea were given on a continuous oral daily schedule for 28 day cycles; imatinib was administered at 400 mg daily to patients not on CYP3A-enzyme inducing antiepileptic drugs (EIAED) while those on EIAED received 500 mg twice a day. All patients received 500 mg twice a day of hydroxyurea. Patients were evaluated every other month with physical and MRI examinations. Results: Twenty-seven patients with recurrent or progressive LGG have enrolled including 17 with astrocytoma and 10 with oligodendroglioma. Eleven (40.7%) are on EIAED. Median age was 42 years (range 24–66 years). 26% of patients had received prior therapy other than surgery (XRT, n=2; chemotherapy, n=5). The most frequent toxicities possibly related to the study regimen were fatigue (grade 2, n=5; grade 3, n=1), neutropenia (grade 2, n=1; grade 3, n=2), anemia (grade 2, n=2), rash (grade 2, n=2), nausea (grade 3, n=1), anorexia (grade 2, n=1), and AST elevation (grade 2, n=1). There were no grade 4 or 5 treatment-related toxicities. Among patients evaluable for response, 17 (85%) achieved stable disease and 3 (15%) had progression. Twenty patients continue on study having received 2–16 months of therapy. Additional accrual and follow-up is ongoing. Conclusions: Continuous daily treatment of imatinib plus hydroxyurea is well tolerated and associated with encouraging preliminary activity among adults with recurrent/progressive LGG. [Table: see text]