Modulation of O6-methylguanine-DNA methyltransferase-mediated nimustine resistance in recurrent malignant gliomas by streptozotocin--a preliminary report.
This trial is based on the strategy of reversing O6-methylguanine-DNA methyltransferase (MGMT)-mediated nimustine resistance by depleting MGMT activity with streptozotocin (STZ) pretreatment. Eight patients with recurrent malignant gliomas refractory to previous nimustine chemotherapy were entered in this study. Patients received STZ (2g/m2) followed one hour with nimustine (2-3 mg/Kg) via the ipsilateral carotid artery. After 1-2 cycles of therapy, 3 patients responded, 4 stabilized, and 1 failed. Toxic effects were generally tolerated. The preliminary results indicated that nimustine-resistant tumor cells in vivo could also be sensitized by modulation of MGMT activity.
Zhao
K M
KM
Department of Neurosurgery, China-Japan Friendship Hospital, Beijing.
Chen
J M
JM
Zuo
H Z
HZ
Wu
Y
Y
Zhang
Y P
YP
D000328:Adult; D001254:Astrocytoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D004351:Drug Resistance; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D006801:Humans; D007269:Injections, Intra-Arterial; D008297:Male; D008780:Methyltransferases / Q000037:antagonists & inhibitors* / Q000502:physiology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D009364:Neoplasm Recurrence, Local; D015376:Nimustine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D019853:O(6)-Methylguanine-DNA Methyltransferase; D012074:Remission Induction; D013311:Streptozocin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
D009363:Neoplasm Proteins; D015376:Nimustine; D013311:Streptozocin; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase