title: A phase 1 study of vinblastine in combination with carboplatin for children with low-grade gliomas: a Children's Oncology Group phase 1 consortium study.
abstract: Both carboplatin and vinblastine have demonstrated single-agent activity in children with low-grade gliomas. A phase 1 trial evaluating 2 different schedules of these 2 agents in combination was performed: (1) Schedule A = carboplatin (140 mg/m(2)) weekly × 3 + vinblastine (4.5 or 3.5 mg/m(2)) weekly × 6, every 6 weeks; (2) Schedule B = carboplatin (300, 400, or 500 mg/m(2)) on day 1 + vinblastine (4.0 mg/m(2)) weekly × 3, every 4 weeks. Twenty-six patients, median (range) age 4.4 (0.7-14.8) years, were enrolled. Four of 9 patients enrolled on Schedule A had recurrent grade 4 neutropenia, suggesting that this schedule was not feasible. Seventeen patients were enrolled on Schedule B. At the 500 mg/m(2) carboplatin dose level, 2 of 3 patients developed dose-limiting toxicity (elevated alkaline phosphatase, neutropenia). At the 400 mg/m(2) carboplatin dose level, none of the 6 patients had dose-limiting toxicity. Ten of 16 patients who received treatment on Schedule B completed the prescribed 12 courses. Of the 21 patients evaluable for response, central review confirmed 1 partial response and 6 minor responses. Eleven patients had stable disease (>3 months) and 3 developed progressive disease. Seven of 9 patients with visual pathway tumors and acute visual changes prior to enrollment had documented improvement. The recommended phase 2 dose and schedule is carboplatin, 400 mg/m(2)/dose on day 1, and vinblastine, 4 mg/m(2)/dose, weekly × 3, repeated every 4 weeks. Further study of this regimen in patients with low-grade glioma is warranted.
authors.affiliation: Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, USA. regina.jakacki@chp.edu
authors.forename: Regina I
authors.initials: RI
authors.lastname: Jakacki
authors.forename: Eric
authors.initials: E
authors.lastname: Bouffet
authors.forename: Peter C
authors.initials: PC
authors.lastname: Adamson
authors.forename: Ian F
authors.initials: IF
authors.lastname: Pollack
authors.forename: Ashish M
authors.initials: AM
authors.lastname: Ingle
authors.forename: Stephan D
authors.initials: SD
authors.lastname: Voss
authors.forename: Susan M
authors.initials: SM
authors.lastname: Blaney
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D020714:Maximum Tolerated Dose; D009367:Neoplasm Staging; D015996:Survival Rate; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D014747:Vinblastine; D016190:Carboplatin