title: Pharmacokinetic investigation of increased efficacy against malignant gliomas of carboplatin combined with hyperbaric oxygenation.
abstract: The efficacy of intravenous administration of 400 mg carboplatin/m(2) body surface area over 60 minutes combined with hyperbaric oxygenation (HBO) therapy (0.2 MPa for 60 min) was investigated in 6 Japanese patients (aged 36-67 years) with malignant or brainstem gliomas. Plasma ultra-filtrate samples were analyzed by high-performance liquid chromatography to evaluate the relationship between efficacy and pharmacokinetics. Brain tumor response was evaluated by magnetic resonance imaging as a function of maximum plasma concentration, area under the curve, or mean residence time (MRT) for carboplatin. The MRT for carboplatin in the complete or partial response group (mean +/- standard deviation 4.3 +/- 1.7 hrs; 6 courses in 3 patients) was significantly longer (p < 0.05) than that in the progressive disease group (2.4 +/- 0.1 hrs; 3 courses in 3 patients), but maximum plasma concentration and area under the curve showed no differences. These results suggest that HBO therapy prolongs the biological residence time of carboplatin. MRT for carboplatin may be useful for predicting continuation or modification of chemotherapy and/or clinical antitumor effects in patients with malignant gliomas.
authors.affiliation: Department of Neurosurgery, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan. y5suzuki@marianna-u.ac.jp
authors.forename: Yu
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Tanaka
authors.forename: Daisuke
authors.initials: D
authors.lastname: Negishi
authors.forename: Makiko
authors.initials: M
authors.lastname: Shimizu
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Takuo
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamazaki
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D020295:Brain Stem Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D004357:Drug Synergism; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D006801:Humans; D006931:Hyperbaric Oxygenation; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000628:therapy; D016879:Salvage Therapy; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D016190:Carboplatin