Skip to main content
Log in

Aspects of cytotoxic drug penetration, with particular reference to anthracyclines

  • Review
  • Anthracyclines, Cytotoxicity
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Summary

Experimental data, particularly derived from tumour spheroids, indicate that drug penetration barriers may be an important determinant of cytotoxic drug efficacay, even in spheroids of only a few hundred microns in diameter. Clinically, tumour masses of this size would equate with those micrometastases which are the target of adjuvant chemotherapy in a wide range of tumour types. It is apparent, therefore, that even at this relatively early stage of the metastatic process, which ultimately proves to be fatal in many patients, measures aimed at improving drug penetration may prove to be crucial in improving the therapeutic efficacy of cytotoxic agents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Dalmark M, Storm HH (1981) A Fickian diffusion transport process with features of transport catalysis. J Gen Physiol 78: 349–364

    Google Scholar 

  2. Durand RE (1981) Flow cytometry studies of intracellular adriamycin in multicell spheroids in vitro. Cancer Res 41: 3495–3498

    Google Scholar 

  3. Eksborg S (1982) Intravesical installation of antineoplastic drugs. Some general aspects. Anthracyclines and Cancer Therapy, 1982, 147–157

  4. Gal D, Ohashi M, MacDonald PC, Buchsbaum HJ, Simpson ER (1981) Low-density lipoprotein as a potential vehicle for chemotherapeutic-agents and radionuclides in the management of gynaecologic neoplasms. Am J Obstet Gynaecol 139: 877–881

    Google Scholar 

  5. Goldacre RJ, Sylven B (1962) On the access of blood-borne deys to various tumour regions. Br J Cancer 16: 306–322

    Google Scholar 

  6. Kaelin WG Jr, Shrivastar S, Shand DG, Jirtle RL (1982) Effect of verapamil on malignant tissue blood flow in SMT-2A tumor bearing rats. Cancer Res 42: 3944–3949

    Google Scholar 

  7. Kaye S, Merry S (1985) Tumour cell resistance to anthracyc-lines — a review. Cancer Chemother Pharmacol 14: 96–103

    Google Scholar 

  8. Legha SS, Benjamin RS, MacKay B, Ewer M, Wallace S, Valdivieso M, Rasmussen SL, Blumenschein GR, Freireich EJ (1982) Reduction of doxorubicin cardiotoxicity by prolonged continous intravenous infussion. Ann Intern Med 96: 133–139

    Google Scholar 

  9. Lowenstein WR (1981) Junctional intercellular communication: the cell-to-cell membrane channel. Phys Rev 61: 829–898

    Google Scholar 

  10. Mattson J, Peterson P (1981) Influence of vasoactive drugs on tumour blood flow. Anticancer Res 1: 59–61

    Google Scholar 

  11. Nederman T, Carlsson J, Malmquist M (1981) Penetration of substances into tumour tissue. A methodological study on cellular spheroids. In Vitro 17: 290–298

    Google Scholar 

  12. Paul C, Gahrton G, Peterson C (1982) Effects of DNA-binding and prolonged infusion on the pharmacokinetics of anthracyclines. Anthracyclines and Cancer Therapy 1982: 18–25

    Google Scholar 

  13. Papadimitriou JM, Woods AE (1974) Structural and functional characteristics of the microcirculation in neoplasms. J Pathol 116: 65–79

    Google Scholar 

  14. Plumb J, Kerr DJ, Wilmott N, Burt AD, More IAR, Kaye SB (1985) Fluorescent microscopic studies on the differential cellular distribution of adriamycin and 4′-deoxydoxorubicin. BACR Abstract 4: 9, Winter Meeting

  15. Powis G (1985) Anticancer drug pharmacodynamics. Cancer Chemother Parmacol 14: 177–183

    Google Scholar 

  16. Sutherland RM, Eddy HA, Bareham B, Reich K, Vanantwerp D (1979) Resistance to adriamycin in multicellular spheroids. Int J Radiat Oncol Biol Phys 5: 1225–1230

    Google Scholar 

  17. Vaupel PW, Frinck S, Bicher HI (1981) Heterogeneous oxygen partial pressure and pH distributionin 3H-mouse mammary adenocarcinoma. Cancer Res 41: 2008–2013

    Google Scholar 

  18. Weinstein RS, Merk FB, Alroy J (1976) The structure and function of intercellular junctions in cancer. In: Klein G, Weinhouse S (eds) Advances in cancer research. Academic, New York, pp 23–84

    Google Scholar 

  19. West GW, Weichselbaum R, Little JB (1980) Limited penetration of methotrexate into human osteosarcoma spheroids as a proposed model for solid tumour resistance to adjuvant chemotherapy. Cancer Res 40: 3665–3668

    Google Scholar 

  20. Wibe E (1980) Resistance to vincristine of human cells grown as multicellular spheroids. Br J Cancer 42: 937–941

    Google Scholar 

  21. Wilson WR, Whitmore GF, Hill RP (1981) Activity of 4′-(9-acridinylamino) methanesulfon-m-anisidide against Chinese hamster cells in multicellular spheroids. Cancer Res 41: 2817–2822

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work was supported by the Cancer Research Campaign

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kerr, D.J., Kaye, S.B. Aspects of cytotoxic drug penetration, with particular reference to anthracyclines. Cancer Chemother. Pharmacol. 19, 1–5 (1987). https://doi.org/10.1007/BF00296245

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00296245

Keywords

Navigation