Synergistic effect between intraneoplastic methotrexate and radiation on experimental intracerebral rat gliosarcoma.
Methotrexate (MTX) alone has a limited effect against malignant brain tumors, but we previously demonstrated a beneficial synergism between MTX and radiation therapy (XRT) against RT-9 gliosarcoma. Because the beneficial effects of that study were limited by systemic toxicity and poor brain penetration of MTX, we have continued our studies using direct intracerebral MTX therapy. Male CD-Fisher rats with intracerebrally implanted RT-9 gliosarcoma and indwelling brain tumor catheters were treated with intracerebral injections of MTX, whole-brain XRT, or a combination of both. MTX was given either as one of two "high-dose" treatments, on the basis of whole-body doses, or two "low-doses," on the basis of average brain weight. MTX alone at lower doses and XRT alone each prolonged survival moderately. High-dose MTX was highly toxic, but low-dose MTX was well tolerated. Combined MTX and XRT caused a significant prolongation of survival in all animals that survived treatment long enough to die from tumor growth.
Wilkinson
H A
HA
Division of Neurosurgery, University of Massachusetts Medical School, Worcester.
Fujiwara
T
T
Rosenfeld
S
S
D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002460:Cell Line; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D004305:Dose-Response Relationship, Drug; D018316:Gliosarcoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D015552:Injections, Intralesional; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000633:toxicity; D009368:Neoplasm Transplantation; D011879:Radiotherapy Dosage; D051381:Rats; D011916:Rats, Inbred F344
D008727:Methotrexate