Phase I study of BCNU and intravenous 6-mercaptopurine in patients with anaplastic gliomas.
On the basis of response rates of up to 50%, BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] is the primary drug used in the chemotherapy of anaplastic gliomas. Preclinical data obtained in several experimental systems show that the cytotoxicity of chloroethylnitrosoureas can be increased by the concomitant use of thiopurines. In this phase I trial, patients with anaplastic gliomas received standard-dose BCNU (200 mg/m2 x 1) in combination with escalating doses of intravenous 6-mercaptopurine (200, 350, 500, and 750 mg/m2 daily x 3), with BCNU being given on day 3 to maximize the effect of the drugs on cellular DNA. No increase in hematologic toxicity was demonstrated as the dose of 6-mercaptopurine was increased. Responses and stabilization of disease were observed in several patients. Due to the safety of and the evidence of activity found for this regimen in the present trial, 750 mg/m2 6-mercaptopurine has been incorporated into subsequent studies.
Smith
D C
DC
Division of Hematology/Oncology, Evanston Hospital, McGaw Medical Center of Northwestern University, Durham, NC.
Vick
N A
NA
Trump
D L
DL
Friedman
H S
HS
Friedman
A H
AH
Purvis
J
J
Gauspari
A
A
Schold
S C
SC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D001933:Brain Stem / Q000473:pathology; D002330:Carmustine / Q000008:administration & dosage; D002648:Child; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D004357:Drug Synergism; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008875:Middle Aged
D015122:Mercaptopurine; D002330:Carmustine