fluorouracil.... 350 to 400 mg/sqm/day IV on days 1 to 5.
leucovorin...... 200 mg/sqm/day IV on days 1 to 5.
FREQUENCY....... Repeat cycle every 21 days.
Machover D. Goldschmidt E. Chollet P. Metzger G. Zittoun
J. Marquet J. Vandenbulcke JM. Misset JL. Schwarzenberg L.
Fourtillan JB. et al. Treatment of advanced colorectal and
gastric adenocarcinomas with 5-fluorouracil and high-dose
folinic acid. Journal of Clinical Oncology. 4(5):685-96, 1986
We report the results of an expanded trial of 5-fluorouracil
(5-FU) combined with high-dose folinic acid for treatment of
patients with advanced colorectal or advanced gastric
adenocarcinoma. In each treatment course, the patients
received both 5-FU (340 to 400 mg/m2/d by intravenous (IV)
infusion for a period of 15 minutes) and folinic acid (200
mg/m2/d by IV bolus) for 5 consecutive days, with a 21-day
interval between courses. Eighty-six patients with colorectal
carcinoma were evaluated. The combined complete and partial
response rates were 39% for 54 patients who did not receive
prior chemotherapy and 22% for 32 patients who had previously
received chemotherapy. Four patients who were previously
resistant to 5-FU attained objective responses. The median
time to disease progression for the 28 responders was 10
months. The median survival time of responders was 19.5
months, and the probability of their being alive at 2 years
was 40%. Of 27 patients with gastric adenocarcinoma, 13 (48%)
responded to therapy. Their median time to disease progression
was 5.5 months. The median survival time of responders was 11
months, and their probability of being alive at 15 months was
30%. Toxicity was within acceptable limits. Toxic effects
included stomatitis, diarrhea, conjunctivitis, skin rash, and
mild myeloid hypoplasia. In a separate study, plasma
concentrations of L-folates greater than 10(-5) mol/L were
achieved after a rapid single IV injection of 200 mg/m2 of
folinic acid. Comparisons of our results with those reported
in previous studies on 5-FU administered as a single agent
suggest that, in advanced colorectal and gastric
adenocarcinoma, folinic acid administered in high doses
enhances the effectiveness of 5-FU administered concomitantly.
Furthermore, some colorectal tumors that were previously
resistant to 5-FU become sensitive to this drug. The survival
of the patients who responded to therapy was markedly improved
over that observed in reported series of untreated patients
with advanced colorectal and gastric adenocarcinomas.