title: 5-FU therapeutic monitoring with dose adjustment leads to an improved therapeutic index in head and neck cancer.
abstract: This 4 year study reports on a pharmacokinetic study for the widely used regimen of cis-platin plus continuous 5-day 5-FU as first-line chemotherapy of head and neck cancer, and the benefit of such data for real-time therapy management. Pharmacokinetic analysis of 177 cycles for 77 patients from a group of 89 patients (group 1; 228 cycles) revealed that both the time-concentration product (AUC) for the entire cycle and the half-cycle AUC (AUC0-3 days) were predictive of cycle toxicity. Real-time analysis of individual AUC0-3 days was used to decide whether to reduce the dose during the second half of the cycle for a total of 249 cycles (81 patients; group 2). The dose in the second half of the course was reduced in 40% of the group 2 courses. There was a statistical difference in complete response rates between group 1 (31%) and group 2 (47%), (0.02 less than P less than 0.05) and a statistically significant reduction was observed in the incidence of toxic cycles (greater than grade 2, group 1 = 20% versus group 2 = 12.4%; 0.02 less than P less than 0.05). Pharmacokinetic follow-up of these patients has proved to be an objective means to improve therapeutic index significantly.
authors.affiliation: Centre Antoine Lacassagne, Nice, France.
authors.forename: J
authors.initials: J
authors.lastname: Santini
authors.forename: G
authors.initials: G
authors.lastname: Milano
authors.forename: A
authors.initials: A
authors.lastname: Thyss
authors.forename: N
authors.initials: N
authors.lastname: Renee
authors.forename: P
authors.initials: P
authors.lastname: Viens
authors.forename: P
authors.initials: P
authors.lastname: Ayela
authors.forename: M
authors.initials: M
authors.lastname: Schneider
authors.forename: F
authors.initials: F
authors.lastname: Demard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies
chemical_list: D005472:Fluorouracil