The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma: a prospective randomized phase III trial. Gastrointestinal Tumor Study Group.
A total of 343 patients with previously untreated metastatic measurable colorectal carcinoma were studied to evaluate the impact on toxicity, response, and survival of leucovorin-modulated fluorouracil (5-FU). A maximally tolerated intravenous bolus loading course regimen of 5-FU alone (500 mg/m2 x 5 days every 4 weeks with 25 mg/m2 escalation) was compared with a high-dose leucovorin regimen (600 mg/m2 of 5-FU with 500 mg/m2 of leucovorin weekly for 6 weeks with a 2-week rest) and with a similar low-dose leucovorin regimen (600 mg/m2 of 5-FU with 25 mg/m2 of leucovorin weekly for 6 weeks with a 2-week rest). The dose-limiting toxicity for the two 5-FU and leucovorin regimens was gastrointestinal, specifically diarrhea; severe diarrhea was seen frequently, and treatment-related toxicity was implicated in the demise of 11 of the patients (5%). Significant improvements in response rates were observed with a response rate of 33 of 109 (30.3%) on the high-dose leucovorin regimen (P less than .01 v control); 13 of 107 (12.1%) on the 5-FU control; and 21 of 112 (18.8%) on the low-dose leucovorin regimen. A trend toward longer survival in the 5-FU plus high-dose leucovorin regimen was observed. In this study, leucovorin was shown to significantly enhance the therapeutic effect of 5-FU in metastatic colorectal carcinoma.
Petrelli
N
N
Roswell Park Memorial Institute, Buffalo, NY.
Douglass
H O
HO
Herrera
L
L
Russell
D
D
Stablein
D M
DM
Bruckner
H W
HW
Mayer
R J
RJ
Schinella
R
R
Green
M D
MD
Muggia
F M
FM
D000368:Aged; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D011446:Prospective Studies; D011897:Random Allocation
D002955:Leucovorin; D005472:Fluorouracil