The EORTC GI group experience with high-dose infusional 5-FU in colorectal cancer.
The EORTC Gastrointestinal Tract Cancer Cooperative Group has conducted a randomized trial of high-dose infusional 5-fluorouracil (FU) with or without Methotrexate (MTX). FU was given as a 48-horus infusion of 60 mg/kg every week x 4, biweekly x 4, and subsequently every 3 weeks. Half of the patients also received 40 mg/m2 MTX as a bolus injection just prior to the FU infusion. A total of 312 patients were randomized. High-dose infusional FU was very well tolerated with virtually no haematological, renal, hepatic or cutaneous toxicity. Nausea and vomiting occurred in 35% and diarrhea in 24% of patients but was almost never severe. Cardiac toxicity and ataxia were seen in less than 5% of patients. Methotrexate lead to a significantly higher incidence of stomatitis, which was severe in 10% of patients. Eleven percent of the high-dose infusional FU patients showed an objective response with stabilization in an additional 35%; median survival was 9.3 months. With the addition of methotrexate a 23% response rate was seen (p = 0.025) and survival was 12.5 months (n.s.). We demonstrated the favorable therapeutic index tolaribility of high-dose (60 mg/kg), short-term (48 hours), frequent (weekly-biweekly) infusional FU and the ability of low-dose MTX to positivity modulate this FU treatment.
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D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D013280:Stomatitis / Q000139:chemically induced / Q000150:complications; D015996:Survival Rate; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil; D008727:Methotrexate