A double-blind comparison of intensive course 5-fluorouracil by oral vs. intravenous route in the treatment of colorectal carcinoma

Abstract

This radomized double-blind study was designed to compare the therapeutic effectiveness of the oral and i.v. routes for 5-FU administered in intensive courses to 100 patients with metastatic adenocarcinoma of the large bowel, treated to equivalent levels of toxicity. An oral dose of 20 mg/kg day times 5 was found to produce comparable G.I., mucocutaneous, and hematologic side effects to a dose of 13.5 mg/kg day times 5 by rapid i.v. injection. Courses were repeated at 5 weeks. Nine of 47, or 19.1%, treated by the oral route have shown objective response, compared to 14 of 53, or 26%, treated by the i.v. route. If malignant hepatomegaly is considered alone, the response rates are 8 of 23, or 34.8%, by the oral route, and 7 of 22, or 31.8%, by the i.v. route. The mean duration of response for the oral group, 11.1 weeks, was shorter than for the i.v. route, 20 weeks, a statistically significant (p less than 0.02) difference. Serial serum 5-FU levels after two doses of 5-FU were determined by microbiological assay in 19 patients. For i.v. administration the curves were comparable among different patients as well as in the same patient. There was striking variability, however, for oral administration.

Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice

“…For example, the oral availability increases from 0 to 80% (Cohen et al, 1974;Hahn et al, 1975;Christophidis et al, 1978;Almersjo et al, 1980) to ϳ100% and the half-life to 5 -6 h (from Ͻ0.5 h). Renal clearance becomes the dominant form of elimination (Baker et al, 1996;Schilsky et al, 1998) for which dose adjustment is easy (based on estimated creatinine clearance).…”

Formulation, in vitro drug release and in vivo human X-ray investigation of polysaccharide based drug delivery systems for targeting 5-fluorouracil to the colon

“…5-Fluorouracil is a pyrimidine analogue and is the drug of choice for colon cancer (Calabresi, Chabner, 1996). Usually it is administered parenterally because absorption after ingestion is unpredictable and incomplete (Hahn et al, 1975). Distribution of 5-fluorouracil to undesired sites produces severe toxic effects of the gastrointestinal, hematological, cardiac, neural and dermatological (Diasio, Harris, 1998).…”

Targeted delivery of an anti-cancer agent via steroid coupled liposomes

“…It interferes with the nucleic acid synthesis and eventually inhibits the cell growth due to its structural resemblance with natural pyrimidines (Langenbach et al, 1972;Parker & Cheng, 1990). The oral bioavailability of the 5-FU is incomplete and erratic, therefore it is administered as an intravenous bolus injection or continuous infusion modulated with folinic acid (leucovorin) (Hahn et al, 1975;Van et al, 1999;Labianca et al, 2001). After intravenous administration, 5-FU may cause severe systemic toxic effects including gastrointestinal, hematological, neural, cardiac, and dermatological when the drug reached the various superfluous sites (Diasio & Harris, 1989).…”