A phase I study of vitamin E, 5-fluorouracil and leucovorin for advanced malignancies.
Six patients with incurable malignancies were originally treated with vitamin E, 3200 IU/day for fourteen days, followed by the same dose of vitamin E daily plus LCV (20 mg/m2 i.v. bolus daily x 5) with 5FU (425 mg/m2 i.v. bolus immediately following LCV). The same schedule of LCV and 5FU was repeated 4 weeks later, then every 5 weeks indefinitely. When 3 of the first 6 had grade 3/4 toxicity, six more patients were treated on the identical drugs and schedule. Seven of twelve total patients had one or more grade 3/4 toxicities. Neutropenia, abdominal pain, and diarrhea were most common. No patient had a documented response, though seven patients did have stable disease. Though the combination of vitamin E and chemotherapy was toxic, this trial demonstrated maximal therapeutic doses of vitamin E can be combined with standard 5FU and LCV, without significantly increasing the side effects of the chemotherapy itself.
Blanke
C D
CD
Department of Medicine, Oregon Health Sciences University, Portland 97232, USA.
Stipanov
M
M
Morrow
J
J
Rothenberg
M
M
Chinery
R
R
Shyr
Y
Y
Coffey
R
R
Johnson
D H
DH
Leach
S D
SD
Beauchamp
R D
RD
D015746:Abdominal Pain / Q000139:chemically induced; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003967:Diarrhea / Q000139:chemically induced; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004305:Dose-Response Relationship, Drug; D028441:F2-Isoprostanes; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D014810:Vitamin E / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D028441:F2-Isoprostanes; D014810:Vitamin E; D015237:Dinoprost; D002955:Leucovorin; D005472:Fluorouracil