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 patien ts with colorectal cancer and 1 patient with breast cancer) during the ir first treatment with 5-fluorouracil (5-FU) plus leucovorin [LV (5-F ULV)]. 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/m(2)) and LV (60 mg/m(2)) 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 mu mol/liter (10 .4-15.1 mu mol/liter; geometric mean with 95% confidence interval of t he mean) to 9.1 mu mol/liter (7.5-11.1 mu mol/liter) in 24 h, tHcy rem ained 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 on ly 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 p atients. Our data establish the reduction of tHcy as a responsive indi cator of LV pharmacodynamics.