Skip to main content

Prediction of normal tissue damage induced by cancer chemotherapy


Cancer chemotherapeutic agents have a low therapeutic index and require a precise and safe presciption. Hematological toxicity is the most common dose limiting side effect of cancer drugs. Therefore, Hemopoietic Stem Cells (HSC) are the most relevant targets for dose determination. Studies of total body irradiation with or without autologous bone marrow transplantation showed that HSC concentrations differe between mouse, rat, rhesus monkey, dog and man. A highly significant correlation was found between bone marrow rescue dose and kg body weight and not between bone marrow rescue dose and BSA. Kg body weight appears to offer a better prescription unit for cancer chemotherapy than BSA, because it correlates better with dose limiting, normal tissue, target cell. This prediction is borne out by the results of chemotherapy in neonates. BSA has also been used as dose unit for drugs with non hematological side effects (e.g., cardiotoxicity of anthracyclines or neurotoxicity of methotrexate). The target for such drug side effects need to be determined before the proper dose unit can be selected. A review of available data shows that for at least some non hematological side effects BSA does not offer the proper prescription unit.

The historical justifications for BSA as dose unit are re-examined (simplicity, correlation with blood volume, correlation with urea under the curve) and considered invalid. The ultimate long term improvements from better prescription methods for cancer chemotherapeutic agents are less normal tissue side effects and better tumor control. The indiscriminate use of BSA as a universal dose unit for cancer chemotherapy would prevent such improvements and is discouraged. Instead, drug doses are to be expressed in units that correlate with dose limiting normal tissue cells.

This is a preview of subscription content, access via your institution.


  1. 1.

    Abramson A, Miller RG, Philips RA (1977) The identification in adult bone marrow of pluripotent and restricted stem cells of the myeloid and lymphoid systems. J Exp Med 145: 1567

    Google Scholar 

  2. 2.

    American Joint Committee on Cancer (1983) Manual for staging of cancer, 2nd edn. Lippincott, Philadelphia, USA

    Google Scholar 

  3. 3.

    Bekkum DW van, van den Engh GJ, Wagemaker G, Bol SJL, Visser JWM (1979) Structural identity of the pluripotential hemopoietic stem cell. Blood Cells 5: 143

    Google Scholar 

  4. 4.

    Bleyer WA (1977) Clinical pharmacology of intrathecal methotrexate. II. An improved dosage regimen derived from agerelated pharmacokinetics. Cancer Treat Rep 6: 1419

    Google Scholar 

  5. 5.

    Bleyer WA (1982) Delayed toxicities of chemotherapy on childhood tissues. Front Radiat Ther Oncol 16: 50

    Google Scholar 

  6. 6.

    Bleyer WA, Coccia PF, Sather HN, Level C, Lukens J, Niebrugge DJ, Siegel S, Littman PS, Leikin SL, Miller DR, Chard RJ JR, Hammond GD, the Children's Cancer Study Group (1983) Reduction in central nervous system leukemia with a pharmacokinetically derived intrathecal methotrexate dosage regimen. J Clin Oncol 1: 317

    Google Scholar 

  7. 7.

    Bond VP, Fliedner TM, Archambeau JD (1965) Mammalian radiation lethality. A disturbance in cellular kinetics. Academic Press, New York

    Google Scholar 

  8. 8.

    Crawford JD, Terry ME, Rourke GM (1950) Simplification of drug dose calculation by application of the surface area principle. Pediatrics 5: 783

    Google Scholar 

  9. 9.

    DeVita VT (1982) Principles of chemotherapy. In: DeVita VT, Hellman S, Rosenberg SA (eds) Cancer, principles and practice of oncology. Lippincott, Philadelphia Toronto, chap 12

    Google Scholar 

  10. 10.

    Dicke KA, Spitzer G, Zander AR (1985) Autologous bone marrow transplantation. Proceedings of the first international symposium, University of Texas, M. D. Anderson Hospital and Tumor Institute, Houston, USA

  11. 11.

    Fliedner TM, Heit H (1969) Hematopoietic death in conventional and germ free mice: In: Bond VP, Sujahara T (eds) Comparative Cellular and Species Radiosensitivity. Igaku Shoin Ltd, Tokyo, Japan, p 220

    Google Scholar 

  12. 12.

    Freireich EJ, Gehan EA, Rall DP, Schmidt LH, Skipper HE (1966) Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey and man. Cancer Chemother Rep 50: 219

    CAS  PubMed  Google Scholar 

  13. 13.

    Goldin A, Carter SK (1982) Screening and evaluation of antitumor agents, Chapter XII-2: In: Holland JF, Frei E. III (eds) Cancer medicine. Lea and Febiger, Philadelphia, p 533

    Google Scholar 

  14. 14.

    Jones B, Breslow NE, Tahashima J (1984) Toxic deaths in The Second National Wilms' Tumor Study. J Clin Oncol 2: 1028

    Google Scholar 

  15. 15.

    Mellet LB (1974) Considerations of concentration and time. Biochem Pharmacol [Suppl] 2: 35

    Google Scholar 

  16. 16.

    Mellet LB (1975) The consistency of the product of concentration and time, Chapter 17: Antineoplastic and immunosupressive agents. In: Sartorelli AC, Johns DG (eds) Handbuch der experimentellen Pharmackologie, vol 38. Springer, Berlin Heidelberg New York, p. 330

    Google Scholar 

  17. 17.

    Metcalf D, Moore MAS (1976) Haemopoietic cells. In: Newberger A, Tatum EL (eds) Frontiers of biology. North Holland, Company, Amsterdam

    Google Scholar 

  18. 18.

    Pinkel D (1958) The use of body surface area as a criterion of drug dosage in cancer chemotherapy. Cancer Res 18: 853

    Google Scholar 

  19. 19.

    Pratt CB, Ransome JL, Evans WE (1978) Age-related adriamycin cardiotoxicity in children. Cancer Treat Rep 62: 1078

    Google Scholar 

  20. 20.

    Quiring P (1955) Surface area determination: In: Glasser E (ed) Medical physics. Year Book Publishers, Chicago, p 1490

    Google Scholar 

  21. 21.

    Schmidt-Nielsen K (1984) Scaling, Why is animal size so important. Cambridge University Press, Cambridge, p 117

    Google Scholar 

  22. 22.

    Siegel SE, Moran PG (1981) Problems in the chemotherapy of cancer in neonates. Am J Radiat Hematol Oncon 3: 287

    Google Scholar 

  23. 23.

    Shaw PJ, Hugh Jones K, Barrett AJ, Desai SJS, Hobbs JR (1985) Experience with busulphan and cyclophosphamide as pre graft conditioning regime in inborn errors of metabolism. (Abstract) Exp Hematol 13 [Suppl] 17: 92

    Google Scholar 

  24. 24.

    Vogelsang NJ (1984) Continuous infusion chemotherapy. J Clin Oncol 2: 1289

    Google Scholar 

  25. 25.

    Von Hoff OD, Layard MW, Basa P, Davis HL, von Hoff AL, Rozenzweig M, Muggia FM (1979) Risk factors for adriamycin-induced congestive heart failure. Ann Intern Med 91: 710

    Google Scholar 

  26. 26.

    Vriesendorp HM (1985) Optimal prescription method for cancer chemotherapy. Exp Hematol 13 [Suppl] 6: 57

    Google Scholar 

  27. 27.

    Vriesendorp HM, van Bekkum DW (1980) Role of total body irradiation in conditioning for bone marrow transplantation: In: Thierfelder S, Rodt H, Kolb JH (eds) Immunobiology of Bone marrow transplantation. Springer, Berlin Heidelberg New York, p. 269

    Google Scholar 

  28. 28.

    Vriesendorp HM, van Bekkum DW (1984) Susceptibility to total body irradiation: In: Broerse JJ, MacVittie TJ (eds) Response of different species to total body irradiation. Amsterdam, p 43

Download references

Author information



Corresponding author

Correspondence to Huib M. Vriesendorp.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Vriesendorp, H.M., Vriesendorp, R. & Vriesendorp, F.J. Prediction of normal tissue damage induced by cancer chemotherapy. Cancer Chemother. Pharmacol. 19, 273–276 (1987).

Download citation


  • Cancer Chemotherapy
  • Total Body Irradiation
  • Autologous Bone Marrow
  • Dose Unit
  • Autologous Bone Marrow Transplantation