title: Irinotecan treatment for recurrent malignant glioma using an every-3-week regimen.
abstract: This phase II study was designed to evaluate the safety, tolerability, and efficacy of irinotecan (CPT-11) in the treatment of adults with malignant glioma. Patients with progressive or recurrent malignant gliomas were enrolled. CPT-11 was administered as a 90-minute intravenous infusion at a dose of 300 mg/m(2) once a week every 3 weeks. After 2 treatments, doses were increased to 350 mg/m(2) in those patients without grade III/IV toxicities. Dose modifications were made for toxicities. All 14 patients who enrolled (11 males and 3 females) were treated with CPT-11 and were assessable for survival, response, and toxicity. The majority of patients (86%) had prior surgery. Two patients had a confirmed partial response and 2 patients (14%) had stable disease. Median survival was 24 weeks. Median time to tumor progression was 6 weeks. The primary hematologic toxicity was grade III/IV neutropenia, which was observed in 14% of patients. Infrequent grade III/IV nonhematologic toxicity was observed, possibly because of the concomitant use of anticonvulsants, which may have altered pharmacokinetics. These results suggest that CPT-11 has activity against recurrent malignant glioma using a dosing regimen of 300 mg/m(2) every 3 weeks showing limited toxicity. The concurrent use of anticonvulsant medications may have played a role in altering pharmacokinetics and thus the maximum tolerated dose in this patient population.
authors.affiliation: UCLA School of Medicine, Henry Singleton Brain Cancer Research Program, Los Angeles, California, USA.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Cloughesy
authors.forename: Emese
authors.initials: E
authors.lastname: Filka
authors.forename: Gillian
authors.initials: G
authors.lastname: Nelson
authors.forename: Fairooz
authors.initials: F
authors.lastname: Kabbinavar
authors.forename: Henry
authors.initials: H
authors.lastname: Friedman
authors.forename: Langdon L
authors.initials: LL
authors.lastname: Miller
authors.forename: Gary L
authors.initials: GL
authors.lastname: Elfring
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D016019:Survival Analysis; D059004:Topoisomerase I Inhibitors
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D000077146:Irinotecan; D002166:Camptothecin