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: J Santini, G Milano, A Thyss, N Renee, P Viens, P Ayela, M Schneider, F Demard
• Journal: British journal of cancer (Br J Cancer) Vol. 59 Issue 2 Pg. 287-90 (Feb 1989) ISSN: 0007-0920 [Print] England
• PMID: 2930694 (Publication Type: Journal Article)

Chemical References

• Fluorouracil

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Squamous Cell (drug therapy)
• Drug Administration Schedule
• Female
• Fluorouracil (administration & dosage, adverse effects, pharmacokinetics)
• Head and Neck Neoplasms (drug therapy)
• Humans
• Male
• Middle Aged
• Prospective Studies
• Retrospective Studies