title: Treosulfan chemotherapy for recurrent malignant glioma.
abstract: Treosulfan is a bifunctional alkylating prodrug with activity against various solid tumors. To improve the outcome for patients with recurrent malignant glioma, we assessed the efficacy of intravenous treosulfan (6-10 g/m2 4-weekly) as salvage therapy for patients with recurrent or progressive glioblastoma (GB, n = 14) or anaplastic astrocytoma (AA, n = 2). All patients had prior involved-field radiotherapy and adjuvant nitrosourea-based chemotherapy. A total of 56 cycles were administered. Tumor responses were assessed radiologically and clinically prior to each cycle. All patients were assessable for toxicity, response and survival. There were no complete or partial responses (CR, PR). Two patients progressed after the first cycle, 14 patients had initially stable disease (SD). Median progression-free survival was 3.25 months for the GB patients. Five patients were progression-free at 6 months (30%), including the 2 AA patients. The 2 AA patients are stable at 22 months. Myelosuppression was the dose-limiting toxicity in this cohort of nitrosourea-pretreated patients. Treosulfan has modest activity in patients with recurrent malignant glioma. Further evaluation of treosulfan in chemonaive malignant glioma patients is warranted.
authors.affiliation: Department of Neurology, University of Tübingen, School of Medicine, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Schmidt
authors.forename: W
authors.initials: W
authors.lastname: Wick
authors.forename: U
authors.initials: U
authors.lastname: Herrlinger
authors.forename: J
authors.initials: J
authors.lastname: Dichgans
authors.forename: M
authors.initials: M
authors.lastname: Weller
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy*; D001853:Bone Marrow / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy*; D002066:Busulfan / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D019233:Retreatment; D016879:Salvage Therapy; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; C018404:treosulfan; D002066:Busulfan