title: A pilot study of metronomic temozolomide treatment in patients with recurrent temozolomide-refractory glioblastoma.
abstract: Frequent regular administration of chemotherapeutic agents at low doses, known as 'metronomic chemotherapy', can increase the anti-angiogenic activity of the drugs, as has been confirmed by several other experimental tumor models. The aim of this pilot study was to evaluate the efficacy and safety of metronomic temozolomide (TMZ) treatment in twelve consecutive patients with recurrent TMZ-refractory glioblastoma. The patients were administered by metronomic treatment schedule (continuous low-dose chemotherapy) with TMZ at a daily dose of 40 mg/m(2). The median overall survival (OS) and progression-free survival (PFS) from the start of metronomic treatment were 11.0 months (95% CI, 5.2-10.5 months) and 6.0 months (95% CI, 0-12.3 months), respectively. During the follow-up period, complete response (CR) was not achieved in any patient, partial response (PR) in 2, and stable disease (SD) in 5 patients. Estimated PFS (CR+PR+SD) was 58.3% at 3 months. Grade III/IV toxicity according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) was not found. These results suggest that the change of chemotherapeutic schedule from conventional to metronomic treatment overcomes the chemo-resistance in patients with recurrent TMZ-refractory glio-blastoma without any major toxicity.
authors.affiliation: Department of Neurosurgery, Samsung Medical Center and Samsung Biomedical Research Institute Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Doo-Sik
authors.initials: DS
authors.lastname: Kong
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Lee
authors.forename: Won Seog
authors.initials: WS
authors.lastname: Kim
authors.forename: Myung Jin
authors.initials: MJ
authors.lastname: Son
authors.forename: Do Hoon
authors.initials: DH
authors.lastname: Lim
authors.forename: Sung Tae
authors.initials: ST
authors.lastname: Kim
authors.forename: Kwan
authors.initials: K
authors.lastname: Park
authors.forename: Jong Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Whan
authors.initials: W
authors.lastname: Eoh
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Nam
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000601:surgery; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010865:Pilot Projects; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide