Long-term weekly treatment of colorectal metastatic cancer with fluorouracil and leucovorin: results of a multicentric prospective trial of fluorouracil dosage optimization by pharmacokinetic monitoring in 152 patients.

• DOI: 10.1200/jco.1998.16.4.1470
• Publication Date: 2017-02-24T10:01:44Z
• Authors: E Gamelin; M Boisdron-Celle; R Delva; C Regimbeau; P E Cailleux; C Alleaume; M L Maillet; M J Goudier; M Sire; M C Person-Joly; M Maigre; P Maillart; R Fety; P Burtin; A Lortholary; Y Dumesnil; L Picon; J Geslin; P Gesta; E Danquechin-Dorval; F Larra; J Robert
• Keywords: Regimen; Therapeutic index

PURPOSE A relationship between fluorouracil (5-FU) dose and response has been previously shown in advanced colorectal cancer. In a previous study with 5-FU stepwise escalation weekly regimen, pharmacokinetic monitoring, we defined therapeutic range for plasma levels: 2,000 to 3,000 microg/L (area under the concentration-time curve at 0 8 hours [AUC0-8], 16 24 mg x h/L). The current investigated intensification individual adjustment multicentric phase II prospective trial. PATIENTS AND METHODS Weekly high-dose was administered by 8-hour infusion 400 mg/m2 leucovorin. initial of (1,300 mg/m2) adapted according levels, reach determined. RESULTS total 152 patients entered from December 1991 1994: 117 measurable metastatic disease 35 assessable disease. Toxicity mainly diarrhea (39%, 5% grade 3) hand-foot syndrome (30%, 2% 3). Among disease, 18 had complete (CR), 48 partial (PR), minor (MR) stable (SD), progressive (PD). Median overall survival time 19 months. rapidly reached variable patient population: mean, 1,803 +/- 386 mg/m2/wk (range, 950 3,396). Thirteen were immediately toxic zone, whereas 51 required > or = 50% increase. CONCLUSION Individual monitoring provided high rate percentage responses, good tolerance.