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 11 trial of low-close 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 11 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, till 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% Cl: 29.30%-35.8%) and the 6-month overall survival was 56.0% (95% Cl: 36.2%-75.8%). One patient developed a grade III neutropenia, grade 11 thrombocytopenia in 3 patients, and grade 11 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 Of all patients included in this study, 4 patients were withdrawn from this study because of side effects including sustained hematological disorders, cryptococcal infection, and cellulitis.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 in effective treatment for recurrent GBM that is even refractory to conventional treatment of TMZ and has acceptable toxicity.