title: Results of phase I study of a multi-modality treatment for newly diagnosed glioblastoma multiforme using local implantation of concurrent BCNU wafers and permanent I-125 seeds followed by fractionated radiation and temozolomide chemotherapy.
abstract: Previously we demonstrated median survival of 69 weeks after combination therapy of permanent, low-activity I-125 seeds and BCNU wafers for recurrent glioblastoma multiforme (GBM). We designed this prospective phase I trial to assess efficacy of this combination treatment for newly diagnosed GBM. Patients with newly diagnosed GBMs deemed amenable to gross total resection were included. This dose-escalation study of I-125 seeds included three 6-patient cohorts, receiving increasing doses of 3000, 6000, and 9000 cGy, and a maximal number of BCNU wafers placed surgically. Postoperatively patients underwent standard fractionated radiation to 5,940 cGy followed by temozolomide chemotherapy. During enrollment of the first 6-patient cohort, the trial was stopped when 3 of 5 patients developed radiation toxicity. Five patients (median age 55 years, range 46-64 years) completed postoperative radiation; Karnofsky Performance Status ranged from 70 to 90. This lowest-dose cohort received I-125 seeds at 3,000 cGy and maximal BCNU wafer placement, and reached endpoint (median 26 weeks follow-up). Two patients developed local disease progression (median 34.4 weeks). The 3 patients who developed radiation toxicity, which was documented on follow-up MRI and confirmed by MRI spectroscopy (median 20 weeks), underwent treatment with steroids and bevacizumab. Our phase I study was closed during enrollment of the first 6-patient cohort because of the high incidence (60 %) of early radiation toxicity. We do not recommend the seed-wafer therapy for newly diagnosed GBM patients but rather reserve this as salvage therapy for select patients with recurrent GBM.
authors.affiliation: Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0515, USA. editor@mayfieldclinic.com
authors.forename: Christopher M
authors.initials: CM
authors.lastname: McPherson
authors.forename: Margie
authors.initials: M
authors.lastname: Gerena-Lewis
authors.forename: John C
authors.initials: JC
authors.lastname: Breneman
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Warnick
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000628:therapy*; D002330:Carmustine / Q000008:administration & dosage; D059248:Chemoradiotherapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis* / Q000628:therapy*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D000077204:Temozolomide
chemical_list: D007457:Iodine Radioisotopes; D003606:Dacarbazine; D002330:Carmustine; D000077204:Temozolomide