A phase 1-2 trial of superselective carboplatin, low-dose infusional 5-fluorouracil and concurrent radiation for high-grade gliomas.
Recent trials have suggested that low-dose infusional 5-FU is more efficacious when given during radiotherapy than is bolus 5-FU. Additionally, intra-arterial cisplatin for brain tumors has been shown to be associated with both high response rates as well as significant toxicity. A dose escalation study was therefore performed using superselective carboplatin, a cisplatin analogue with a favorable CNS toxicity profile in combination with 6 weeks of infusional 5-FU at 225 mg/m2 and concurrent radiotherapy. Eight patients were treated at the starting dose of 200 mg/m2 carboplatin and 11 patients were treated at 300 mg/m2. No toxicity was observed that was attributable to infusional 5-FU. However, two ischemic events related to the superselective delivery of carboplatin were observed, and one patient was noted to have asymptomatic retinal toxicity from the carboplatin. Of 19 patients, 5 had objective responses with 25% or greater reduction in tumor volumes. Continuous infusional 5-FU can be given in combination with partial brain radiotherapy without significant toxicity. Superselective carboplatin delivery is associated with a low incidence of stroke, but no significant retinal toxicity.
Department of Radiology, University of Virginia Health Sciences Center, Charlottesville 22908.
J M
JM
Larner
C D
CD
Phillips
J E
JE
Dion
M E
ME
Jensen
S A
SA
Newman
J A
JA
Jane
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D016190:Carboplatin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005909:Glioblastoma / Q000628:therapy; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis; D016896:Treatment Outcome
D016190:Carboplatin; D005472:Fluorouracil