A pilot study of metronomic temozolomide treatment in patients with recurrent temozolomide-refractory glioblastoma.
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.
Kong
Doo-Sik
DS
Department of Neurosurgery, Samsung Medical Center and Samsung Biomedical Research Institute Sungkyunkwan University School of Medicine, Seoul, Korea.
Lee
Jung-Il
JI
Kim
Won Seog
WS
Son
Myung Jin
MJ
Lim
Do Hoon
DH
Kim
Sung Tae
ST
Park
Kwan
K
Kim
Jong Hyun
JH
Eoh
Whan
W
Nam
Do-Hyun
DH
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
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide