Phase II trial of low-dose continuous (metronomic) treatment of temozolomide for recurrent glioblastoma.
The prognosis for patients with recurrent glioblastomas (GBMs) is dismal, with a median survival of 3-6 months. We performed a phase II trial of low-dose continuous (metronomic) treatment using temozolomide (TMZ) for recurrent GBMs. TMZ-refractory patients with GBM who experienced disease recurrence or progression during or after the cyclic treatment schedule of TMZ after surgery and standard radiotherapy were eligible. This phase II trial included 2 cohorts of patients. The initial cohort, comprising 10 patients, received TMZ at 40 mg/m(2) everyday. After this regimen seemed safe and effective, the metronomic schedule was changed to 50 mg/m(2) everyday. The second cohort, comprising 28 patients, received TMZ at 50 mg/m(2) everyday. The 6-month progression-free survival in all 38 patients was 32.5% (95% CI: 29.3%-35.8%) and the 6-month overall survival was 56.0% (95% CI: 36.2%-75.8%). One patient developed a grade III neutropenia, grade II thrombocytopenia in 3 patients, and grade II increase of liver enzyme (GOT/GPT) in 3 patients. Of all patients included in this study, 4 patients were withdrawn from this study because of side effects including sustained hematological disorders, cryptococcal infection, and cellulitis. In a response group, quality of life measured with short form-36 was well preserved, when compared with the pretreatment status. Metronomic treatment of TMZ is an effective treatment for recurrent GBM that is even refractory to conventional treatment of TMZ and has acceptable toxicity.
Kong
Doo-Sik
DS
Department of Neurosurgery, Samsung Medical Center, Seoul, Korea.
Lee
Jung-Il
JI
Kim
Jong Hyun
JH
Kim
Sung Tae
ST
Kim
Won Seog
WS
Suh
Yeon-Lim
YL
Dong
Seung Myung
SM
Nam
Do-Hyun
DH
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D016133:Polymerase Chain Reaction; D011788:Quality of Life; D000077204:Temozolomide; D055815:Young Adult
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide