Changes in folate status as determined by reduction in total plasma homocysteine levels during leucovorin modulation of 5-fluorouracil therapy in cancer patients.
We measured plasma total homocysteine (tHcy) in 14 patients (13 patients with colorectal cancer and 1 patient with breast cancer) during their first treatment with 5-fluorouracil (5-FU) plus leucovorin [LV (5-FULV)]. Eight of these patients were investigated a second time after 3-10 cycles (median, 4 cycles) with 5-FULV. Each cycle consisted of two administrations of 5-FU (500 mg/m2) and LV (60 mg/m2) given 24 h apart. The first administration of 5-FULV on day 1 of the first cycle induced a rapid reduction of the tHcy level from 12.5 micromol/liter (10.4-15.1 micromol/liter; geometric mean with 95% confidence interval of the mean) to 9.1 micromol/liter (7.5-11.1 micromol/liter) in 24 h. tHcy remained stable at this level after the second administration of 5-FULV. In addition, the 5-FULV regimen caused a concurrent 4-fold increase in both serum and erythrocyte folate. The fifth cycle with 5-FULV had only marginal effects on the tHcy level. 5-FU without LV modulation had no effect on the plasma tHcy or folate status in eight breast cancer patients. Our data establish the reduction of tHcy as a responsive indicator of LV pharmacodynamics.
Geisler
J
J
Department of Oncology, Haukeland University Hospital, Bergen, Norway.
Geisler
S B
SB
Lønning
P E
PE
Smaaland
R
R
Tveit
K M
KM
Refsum
H
H
Ueland
P M
PM
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy*; D003404:Creatinine / Q000097:blood; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005492:Folic Acid / Q000097:blood*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D014805:Vitamin B 12 / Q000097:blood
D006710:Homocysteine; D005492:Folic Acid; D003404:Creatinine; D014805:Vitamin B 12; D002955:Leucovorin; D005472:Fluorouracil