A phase II study of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brainstem gliomas: a Pediatric Brain Tumor Consortium study

作者：Warren Katherine E^*; Gururangan Sri; Geyer J Russell; McLendon Roger E; Poussaint Tina Young; Wallace Dana; Balis Frank M; Berg Stacey L; Packer Roger J; Goldman Stewart; Minturn Jane E; Pollack Ian F; Boyett James M; Kun Larry E

来源：Journal of Neuro-Oncology, 2012, 106(3): 643-649.

DOI：10.1007/s11060-011-0709-z

• Glioma
• Pediatric
• Resistance
• Alkylating agent
• Brainstem glioma
• AGT
• MGMT

To estimate the sustained (a parts per thousand yen8 weeks) objective response rate in pediatric patients with recurrent or progressive high-grade gliomas (HGG, Stratum A) or brainstem gliomas (BSG, Stratum B) treated with the combination of O6-benzylguanine (O6BG) and temozolomide(A (R)) (TMZ). Patients received O6BG 120 mg/m(2)/d IV followed by TMZ 75 mg/m(2)/d orally daily for 5 consecutive days of each 28-day course. The target objective response rate to consider the combination active was 17%. A two-stage design was employed. Forty-three patients were enrolled; 41 were evaluable for response, including 25 patients with HGG and 16 patients with BSG. The combination of O6BG and TMZ was tolerable, and the primary toxicities were myelosuppression and gastrointestinal symptoms. One sustained (a parts per thousand yen8 weeks) partial response was observed in the HGG cohort; no sustained objective responses were observed in the BSG cohort. Long-term (a parts per thousand yen6 courses) stable disease (SD) was observed in 4 patients in Stratum A and 1 patient in Stratum B. Of the 5 patients with objective response or long-term SD, 3 underwent central review with 2 reclassified as low-grade gliomas. The combination of O6BG and TMZ did not achieve the target response rate for activity in pediatric patients with recurrent or progressive HGG and BSG.

• 出版日期2012-2