Treatment of cancer with weekly intravenous 5-fluorouracil.Study by the Western Cooperative Cancer Chemotherapy Group (WCCCG)

Abstract

5‐Fluorouracil (5‐FU) has usually been administered by rapid intravenous injection of 15 mg/kg daily for 3‐5 days and 7.5 mg/kg every 2 or 3 days to toxicity, repeated monthly (antitumor response about 10‐30%). Drug morbidity and mortality have been excessive. Modifications of this course have shown similar response rates but decreased toxicity and mortality. In the present WCCCG study, 548 patients with disseminated cancer were treated weekly with 5‐FU, without a loading dose, by rapid intravenous injection, beginning at 15 mg/kg/week for one month, and increased to 20 mg/kg/week (if necessary) to levels producing mild toxicity or an antitumor effect. Of the 339 patients now evaluated for response, 6 had complete responses, 54 had decreases in tumor size > 50%, and 34 had decreases in tumor size of 25‐50%. The response rates > 50% (I‐B and I‐C) for adenocarcinoma of the breast, stomach, and colon were 37.8%, 28.6%, and 16%, respectively. Of the 430 patients evaluated for toxicity, 62 manifested no toxicity, and 368 patients had mild‐to‐severe toxicity. There were 8 drug‐related deaths in patients who received 5‐FU in dosages higher than those allowed in the protocol. There were no drug deaths in patients who received 5‐FU as stipulated by the protocol.

Personalizing Colon Cancer Therapeutics: Targeting Old and New Mechanisms of Action

“…Unfortunately, tumor regression was only observed when toxic 5-FU concentrations were used. Thus, for decades, studies have been done to optimize the dose [7], schedule [8,9,10] and mode of administration [11,12] to maximize therapeutic effect and minimize toxicity. Currently, 5-FU is administered with leucovorin in regimens that consist of combinations of bolus injection and continuous intravenous infusions.…”

Radiotherapy and Chemotherapy for Colorectal Cancer [Abridged]

“…as a single intravenous injection once every week or two weeks. There are valid reasons, theoretical (Bruce et al 1966) and practical (Jacobs et al 1971), for this dose schedule. The practice of giving the drug daily for several days or until toxicity supervenes should be abandoned; it has no therapeutic advantage and often makes the patient worse than he would be without treatment.…”