Advertisement

Basic Investigations on Interaction of 5-Fluorouracil and Tumor Ischemia in the Treatment of Liver Malignancies

  • B. Eibl-Eibesfeldt
  • V. Storz
  • J. Kummermehr
  • A. Schalhorn
Conference paper
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 110)

Abstract

Pharmacokinetic considerations are the main rationale for locoregional treatment of hepatic malignancies with anticancer drugs [3, 6,10]. The advantage of regional exposure of arterially infused drugs increases when the blood flow rate into the target region is reduced [6,13]. Impairment of tumor blood flow and synchronous intra-arterial chemotherapy have been employed in various clinical studies using 5-fluorouracil (5-FU) [8, 9, 18]. The antimetabolite 5-FU is activated in the tumor cell, requiring several energy-dependent anabolic steps (Fig. 1). This applies to the drug’s action on RNA as well as DNA synthesis [14, 17]. Whether active carrier-mediated transport into the tumor cell of 5-FU is also involved is still a matter of discussion [17].

Keywords

Time Lapse Basic Investigation Tumor Blood Flow Regional Exposure Starch Microsphere 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Chabner BA, Myers CE (1985) Clinical pharmacology of cancer chemotherapy. In: de-Vita V, Hellman S, Rosenberg SA (eds) Principles and practice of oncology, vol 1, 2nd edn. Lippincott, Philadelphia, pp 287–328Google Scholar
  2. 2.
    Chadwick M, Rogers WJ (1972) The physiological distribution of 5-fluorouracil in mice bearing solid L 1210 lymphocytic leukemia. Cancer Res 32: 1045–1056PubMedGoogle Scholar
  3. 3.
    Chen HSG, Gross JF (1980) Intra-arterial infusion of anticancer drugs: theoretic aspects of drug delivery and review of responses. Cancer Treat Rep 64: 31–40PubMedGoogle Scholar
  4. 4.
    Eibl-Eibesfeldt B, Brunner K, Pfeifer KJ, Schweiberer L, Geissler K (1984) Repeated ischemia and metachron cytostatic therapy in the treatment of liver metastases: a new application of degradable starch microspheres. Conference on therapeutic strategies in primary and metastatic liver cancer, Heidelberg, Sept. 17–19Google Scholar
  5. 5.
    Eibl-Eibesfeldt B, Pfeifer KJ, Wilker D, Hohner E, Bassermann R (1985) Starch microspheres embolisation and metachron cytostatic therapy: a new method of temporary liver dearterialisation. 2nd Int conf on advances in regional cancer therapy, Gießen, p 87 (Abstract)Google Scholar
  6. 6.
    Ensminger WD, Gyves JW (1983) Clinical pharmacology of hepatic arterial chemotherapy. Sem Oncol 10(2): 176–182Google Scholar
  7. 7.
    Ensminger WD, Rosowsky A, Raso, V (1978) A clinical pharmacological evaluation of hepatic arterial infusion of 5-fluoro-2’-desoxyuridine and 5-fluorouracil. Cancer Res 38: 3784–3792PubMedGoogle Scholar
  8. 8.
    Hansen H (1984) Erste Ergebnisse der Therapie multipler Lebermetastasen durch passagère Leberdearterialisation und intraarterielle Chemotherapie. Langenbecks Arch Chir [Suppl Chir Forum]: 295–298Google Scholar
  9. 9.
    Helmer RE, Morettin LB, Costanzi JJ (1981) Hepatic artery occlusion with perfusion in the treatment of carcinoid syndrome. Oncology 38: 361–364PubMedCrossRefGoogle Scholar
  10. 10.
    Howell SR (1985) Pharmacokinetic principles of intra-arterial therapy. 2nd Int Conf on advances in regional cancer therapy, Gießen, p 3 (Abstracts)Google Scholar
  11. 11.
    Jones DP (1981) Hypoxia and drug metabolism. Biochem Pharmacol 30: 1019–1023PubMedCrossRefGoogle Scholar
  12. 12.
    Laskin JD, Evans RM, Slocium HK, Burke D, Hakala MT (1979) Basis for natural variation in sensitivity to 5-fluorouracil in mouse and human cells in culture. Cancer Res 39: 383–390PubMedGoogle Scholar
  13. 13.
    Lindberg B, Lote K, Teder H (1984) Biodegradable starch microspheres — a new medical tool. In: Davis SS, McVie JG, Tomlinson E (eds) Microspheres and drug therapy. Pharmaceutical, immunological and medical aspects. Elsevier, AmsterdamGoogle Scholar
  14. 14.
    Myers ChE (1981) The pharmacology of the fluoropyrimidines. Pharmacol Rev 33:1–15PubMedGoogle Scholar
  15. 15.
    Tannock J (1978) Cell kinetics and chemotherapy: a critical review. Cancer Treat Rep 62: 1117–1133PubMedGoogle Scholar
  16. 16.
    Thomlinson RH, Craddock EA (1967) The gross response of an experimental tumor to single doses of X-rays. Br J Cancer 21: 107–123CrossRefGoogle Scholar
  17. 17.
    Valeriote F, Santelli G (1984) 5-fluorouracil (FUra). Pharmacol Ther 24: 107–132PubMedCrossRefGoogle Scholar
  18. 18.
    Wopfner F (1983) Intra-arterial chemotherapy of the liver with transient repeated hypoxia. In: Schwemmle K, Aigner K (eds) Vascular perfusion in cancer therapy. Springer, Berlin Heidelberg New York Tokyo, pp 75–82 (Recent results in cancer research, vol 86)Google Scholar
  19. 19.
    DeVita VT (1971) Cell kinetics and the chemotherapy of cancer. Cancer Chemother Rep 2:23–33Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • B. Eibl-Eibesfeldt
    • 1
  • V. Storz
    • 1
  • J. Kummermehr
    • 1
  • A. Schalhorn
    • 1
  1. 1.Chirurgische Klinik Innenstadt und Chirurgische PoliklinikUniversität MünchenMünchen 2Germany

Personalised recommendations