Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1989 Feb;59(2):287–290. doi: 10.1038/bjc.1989.59

5-FU therapeutic monitoring with dose adjustment leads to an improved therapeutic index in head and neck cancer.

J Santini 1, G Milano 1, A Thyss 1, N Renee 1, P Viens 1, P Ayela 1, M Schneider 1, F Demard 1
PMCID: PMC2247002  PMID: 2930694

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.

Full text

PDF
287

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allen L. M. Pharmacokinetic principles of antineoplastic drug therapy. J Clin Pharmacol. 1983 Feb-Mar;23(2-3):71–81. doi: 10.1002/j.1552-4604.1983.tb02707.x. [DOI] [PubMed] [Google Scholar]
  2. Amrein P. C., Weitzman S. A. Treatment of squamous-cell carcinoma of the head and neck with cisplatin and 5-fluorouracil. J Clin Oncol. 1985 Dec;3(12):1632–1639. doi: 10.1200/JCO.1985.3.12.1632. [DOI] [PubMed] [Google Scholar]
  3. Buroker T. R., Moertel C. G., Fleming T. R., Everson L. K., Cullinan S. A., Krook J. E., Mailliard J. A., Marschke R. F., Klaassen D. J., Laurie J. A. A controlled evaluation of recent approaches to biochemical modulation or enhancement of 5-fluorouracil therapy in colorectal carcinoma. J Clin Oncol. 1985 Dec;3(12):1624–1631. doi: 10.1200/JCO.1985.3.12.1624. [DOI] [PubMed] [Google Scholar]
  4. Christophidis N., Mihaly G., Vajda F., Louis W. Comparison of liquid- and gas-liquid chromatographic assays of 5-fluorouracil in plasma. Clin Chem. 1979 Jan;25(1):83–86. [PubMed] [Google Scholar]
  5. Kies M. S., Rosen S. T., Tsang T. K., Shetty R., Schneider P. A., Wallemark C. B., Shields T. W. Cisplatin and 5-fluorouracil in the primary management of squamous esophageal cancer. Cancer. 1987 Nov 1;60(9):2156–2160. doi: 10.1002/1097-0142(19871101)60:9<2156::aid-cncr2820600906>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  6. Kish J., Drelichman A., Jacobs J., Hoschner J., Kinzie J., Loh J., Weaver A., Al-Sarraf M. Clinical trial of cisplatin and 5-FU infusion as initial treatment for advanced squamous cell carcinoma of the head and neck. Cancer Treat Rep. 1982 Mar;66(3):471–474. [PubMed] [Google Scholar]
  7. Merlano M., Grimaldi A., Brunetti I., Modenesi M., Scala M., Margarino G., Scasso F., Santelli A., Castiglia G., Pallestrini E. Simultaneous cisplatin and 5-fluorouracil as second-line treatment of head and neck cancer. Cancer Treat Rep. 1987 May;71(5):485–488. [PubMed] [Google Scholar]
  8. Myers C. E. The pharmacology of the fluoropyrimidines. Pharmacol Rev. 1981 Mar;33(1):1–15. [PubMed] [Google Scholar]
  9. Powis G. Anticancer drug pharmacodynamics. Cancer Chemother Pharmacol. 1985;14(3):177–183. doi: 10.1007/BF00258112. [DOI] [PubMed] [Google Scholar]
  10. Rooney M., Kish J., Jacobs J., Kinzie J., Weaver A., Crissman J., Al-Sarraf M. Improved complete response rate and survival in advanced head and neck cancer after three-course induction therapy with 120-hour 5-FU infusion and cisplatin. Cancer. 1985 Mar 1;55(5):1123–1128. doi: 10.1002/1097-0142(19850301)55:5<1123::aid-cncr2820550530>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  11. Sulkes A., Collins J. M. Reappraisal of some dosage adjustment guidelines. Cancer Treat Rep. 1987 Mar;71(3):229–233. [PubMed] [Google Scholar]
  12. Thyss A., Falewee M. N., Leborgne L., Viens P., Schneider M., Demard F. Cardiotoxicité du 5 fluoro-uracile. Spasme ou toxicité myocardique directe? Bull Cancer. 1987;74(4):381–385. [PubMed] [Google Scholar]
  13. Thyss A., Milano G., Renée N., Vallicioni J., Schneider M., Demard F. Clinical pharmacokinetic study of 5-FU in continuous 5-day infusions for head and neck cancer. Cancer Chemother Pharmacol. 1986;16(1):64–66. doi: 10.1007/BF00255288. [DOI] [PubMed] [Google Scholar]
  14. Weiss H. D., Walker M. D., Wiernik P. H. Neurotoxicity of commonly used antineoplastic agents (first of two parts). N Engl J Med. 1974 Jun 11;291(2):75–81. doi: 10.1056/NEJM197407112910205. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES