Acta Neurochirurgica

, Volume 104, Issue 1–2, pp 13–16 | Cite as

Uptake of Adriamycin in tumour and surrounding brain tissue in patients with malignant gliomas

  • H. von Holst
  • E. Knochenhauer
  • H. Blomgren
  • V. P. Collins
  • L. Ehn
  • M. Lindquist
  • G. Norén
  • C. Peterson
Clinical Research

Summary

Eight patients with malignant gliomas verified on CT scan, received an intravenous injection of 50 mg of Adriamycin R, 24 hours prior to surgical removal of the tumour. Peroperatively, both tumour and surrounding tissue specimens were obtained for determination of the tissue concentrations of Adriamycin and its reduced metabolite Adriamycinol. It was found that Adriamycin could be detected in tumour tissue from all patients. The concentration varied between 0,9 and 4,6 nmol/g tissue. In contrast, Adriamycin could only be detected in surrounding brain tissue from one patient.

In anin vitro study a human malignant glioma cell line (U-251 MG) was exposed to various concentrations of Adriamycin for 24 hours. It was found that an intracellular drug concentration above 30 nmol/g cells caused a concentration dependent inhibition of cell growth. Thus, it is likely that the poor effect of Adriamycin on patients with malignant gliomas is due to an ineffective drug accumulation in the tumour tissue.

Keywords

Adriamycin malignant gliomas glioblastoma chemotherapy tissue concentration 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Edwards MS, Levin VA, Wilson CB (1980) Brain tumour chemotherapy evaluation of agents in current use for phase II and III trials. Cancer Treat Rep 64: 1179–1205PubMedGoogle Scholar
  2. 2.
    Di Marco A (1975) Adriamycin (NSC-123127): Mode and mechanism of action. Cancer Chemother Rep Part III 6: 91–106Google Scholar
  3. 3.
    Benjamin RS, Wiernek PH, Bachur NR (1974) Adriamycin chemotherapy-efficacy, safety, and pharmacologic basis of an intermittent single high-dose schedule. Cancer 33: 19–27PubMedGoogle Scholar
  4. 4.
    Boustelle CT, Uari SH, Rekate H (1983) Intracarotid chemotherapy of glioblastomas after induced blood-brain barrier disruption. AJNR 4 (3): 810–812PubMedGoogle Scholar
  5. 5.
    Nakazawa S, Itoh Y (1983) New management of brain neoplasms: Local injection of Adriamycin. No Shinkei Geko 11 (8): 821–827Google Scholar
  6. 6.
    Peterson C, Paul C, Gahrton G (1981) Anthracycline-DNA complexes as slow release preparations in the treatment of acute leukemia. In: Lewis DH (ed) Controlled release of pesticides and pharmaceuticals. Plenum Publishing Corporation, New York, pp 49–65Google Scholar
  7. 7.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275PubMedGoogle Scholar
  8. 8.
    Sakai N, Kondo H, Shikinami A, Hirata T, Funakoshi T, Tanabe Y, Yamada H (1984) Postoperative treatment for malignant intracranial tumours —especially concerning intermittent intracarotid administration of Adriamycin (in Japanese). No Shinkei Geko 12: 237–243Google Scholar
  9. 9.
    Peterson C, Gunvén P, Theve NO (1986) Comparative pharmacokinetics of doxorubicin and epirubicin in patients with gastrointestinal cancer. Cancer Treat Rep 70: 947–952PubMedGoogle Scholar
  10. 10.
    Pastan I, Gottesman M (1987) Multiple-drug resistance in human cancer. N Engl J Med 316: 1388–1393PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • H. von Holst
    • 1
  • E. Knochenhauer
    • 2
  • H. Blomgren
    • 3
  • V. P. Collins
    • 4
  • L. Ehn
    • 3
  • M. Lindquist
    • 5
  • G. Norén
    • 1
  • C. Peterson
    • 2
  1. 1.Department of NeurosurgeryLudwig Institute for Cancer ResearchStockholm
  2. 2.Department of Clinical PharmacologyLudwig Institute for Cancer ResearchStockholm
  3. 3.Department of OncologyLudwig Institute for Cancer ResearchStockholm
  4. 4.Department of Branch and Tumour PathologyKarolinska HospitalStockholmSweden
  5. 5.Department of NeuroradiologyKarolinska HospitalStockholmSweden

Personalised recommendations