© 2004 by Society
© 2004 by the Society forNeuro-Oncology
Phase 2 trial of BCNU plus irinotecan in adults with malignantglioma
Departments of Surgery (D.A.R., J.A.Q., J.N.R., S.G.,J.V., J.H.S., A.W., M.B., S.T.-U., M.L.A., S.J., D.A., K.Z., S.S., C.B.,A.H.F., D.D.B., H.S.F.), Neurology (J.A.Q.,J.N.R.), Pediatrics (D.A.R., S.G., H.S.F.), Radiology (J.M.P.), Cancer CenterBiostatistics (J.E.H., J.M.D.), and Pathology(D.D.B.), Duke University Medical Center, Durham, NC 27710, USA
2 Address correspondence to David A. Reardon, The Brain Tumor Center at Duke,Duke University Medical Center, Box 3624, Durham, NC 27710(reard003{at}mc.duke.edu).
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In preclinical studies, BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, plusCPT-11 (irinotecan) exhibits schedule-dependent, synergistic activity againstmalignant glioma (MG). We previously established the maximum tolerated dose ofCPT-11 when administered for 4 consecutive weeks in combination with BCNUadministered on the first day of each 6-week cycle. We now report a phase 2trial of BCNU plus CPT-11 for patients with MG. In the current study, BCNU(100 mg/m2) was administered on day 1 of each 6-week cycle. CPT-11was administered on days 1, 8, 15, and 22 at 225 mg/m2 for patientsreceiving CYP3A1- or CYP3A4-inducing anticonvulsants and at 125mg/m2 for those not on these medications. Newly diagnosed patientsreceived up to 3 cycles before radiotherapy, while recurrent patients receivedup to 8 cycles. The primary end point of this study was radiographic response,while time to progression and overall survival were also assessed. Seventy-sixpatients were treated, including 37 with newly diagnosed tumors and 39 withrecurrent disease. Fifty-six had glioblastoma multiforme, 18 had anaplasticastrocytoma, and 2 had anaplastic oligodendroglioma. Toxicities (grade 
3)included infections (13%), thromboses (12%), diarrhea (10%), and neutropenia(7%). Interstitial pneumonitis developed in 4 patients. Five newly diagnosedpatients (14%; 95% CI, 5%-29%) achieved a radiographic response (1 completeresponse and 4 partial responses). Five patients with recurrent MG alsoachieved a response (1 complete response and 4 partial responses; 13%; 95% CI,4%-27%). More than 40% of both newly diagnosed and recurrent patients achievedstable disease. Median time to progression was 11.3 weeks for recurrentglioblastoma multiforme patients and 16.9 weeks for recurrent anaplasticastrocytoma/anaplastic oligodendroglioma patients. We conclude that theactivity of BCNU plus CPT-11 for patients with MG appears comparable to thatof CPT-11 alone and may be more toxic.
Received July 30, 2003; Accepted December 4, 2003
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