title: Phase I/II Study of Temozolomide Plus Nimustine Chemotherapy for Recurrent Malignant Gliomas: Kyoto Neuro-oncology Group.
abstract: The objective of this phase I/II study was to examine the efficacy and toxicity profile of temozolomide (TMZ) plus nimustine (ACNU). Patients who had received a standard radiotherapy with one or two previous chemo-regimens were enrolled. In phase I, the maximum-tolerated dose (MTD) by TMZ (150 mg/m2/day) (Day 1-5) plus various doses of ACNU (30, 35, 40, 45 mg/m2/day) (Day 15) per 4 weeks was defined on a standard 3 + 3 design. In phase II, these therapeutic activity and safety of this regimen were evaluated. Forty-nine eligible patients were enrolled. The median age was 50 years-old. Eighty percent had a KPS of 70-100. Histologies were glioblastoma (73%), anaplastic astrocytoma (22%), anaplastic oligodendroglioma (4%). In phase I, 15 patients were treated at four cohorts by TMZ plus ACNU. MTD was TMZ (150 mg/m2) plus ACNU (40 mg/m2). In phase II, 40 patients were treated at the dose of cohort 3 (MTD). Thirty-five percent of patients experienced grade 3 or 4 toxicities, mainly hematologic. The overall response rate was 11% (4/37). Sixty-eight percent (25/37) had stable disease. Twenty-two percent (8/37) showed progression. Progression-free survival (PFS) rates at 6 and 12 months were 24% (95% CI, 12-35%) and 8% (95% CI, 4-15%). Median PFS was 13 months (95% CI, 9.2-17.2 months). Overall survival (OS) at 6 and 12 were 78% (95% CI, 67-89%) and 49% (95% CI, 33-57%). Median OS was 11.8 months (95% CI, 8.2-14.5 months). This phase I/II study showed a moderate toxicity in hematology and may has a promising efficacy in OS, without inferiority in PFS.
authors.affiliation: Department of Neurosurgery, National Hospital Organization, Kyoto Medical Center.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Aoki
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Arakawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ueba
authors.forename: Masashi
authors.initials: M
authors.lastname: Oda
authors.forename: Namiko
authors.initials: N
authors.lastname: Nishida
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tsukahara
authors.forename: Koichi
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Mikuni
authors.forename: Susumu
authors.initials: S
authors.lastname: Miyamoto
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D015376:Nimustine / Q000627:therapeutic use*; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D015376:Nimustine; D003606:Dacarbazine; D000077204:Temozolomide