Double modulation of 5-fluorouracil in the treatment of advanced colorectal carcinoma: report of a trial with sequential methotrexate, intravenous (loading dose) folinic acid, 5-fluorouracil, and a literature review.
5-Fluorouracil (5-FU) modulation with either folinic acid (FA) or methotrexate (MTX) has improved 5-FU's potential cytoreductivity. We combined MTX and FA with 5-FU to further augment 5-FU's cytoreductivity. Patients (n = 34) with advanced colorectal carcinoma were first given intravenous MTX (escalated from 30 mg/m2 to 70 mg/m2). FA (100 mg/m2) was infused 17-24 hr later, followed by 5-FU (600 mg/m2). Oral rescue doses of FA were begun 24 hr after MTX. Patients were treated every 2 weeks. No previously treated patient (n = 6) responded. Eight of the remaining 28 (29%) (95% confidence interval, 15-47%) patients achieved a PR. Median survival was 9.3 months. Toxicity (primarily gastrointestinal) necessitated dosage modification in 10 patients (29%). These results, in addition to a literature review, reveal that the manipulation of 5-FU by two modulating agents does not improve the response rate seen with single-agent modulation.
Balaban
E P
EP
Department of Internal Medicine, Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas.
Graham
M
M
Perkins
S
S
Sheehan
R G
RG
Frenkel
E P
EP
Ross
M
M
Bull
J
J
Pruitt
B
B
Periman
P
P
Ruud
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome
D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate