Skip to main content
SpringerLink
Log in

Penetration of Idarubicin into Malignant Brain Tumor Tissue

  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Anthracyclines are effective in breast cancer and have in vitro cytotoxicity in glioma. In patients with glioma anthracyclines are not effective possibly because the hydrophilic drugs do not reach cytotoxic levels in tumor tissue. Idarubicin is more lipophilic than the other anthracyclines and is more cytotoxic in glioma cell lines. The uptake of idarubicin and its major metabolite idarubicinol in brain tumor tissue were measured in a patient with a brain metastasis from breast cancer and in 4 patients with malignant glioma after an oral dose of idarubicin (45 mg/m2 in 1 patient; 25 mg/m2 in 4 patients), given 15–24 h before brain tumor resection. The concentrations of idarubicin and of idarubicinol in tumor tissue exceeded the concurrent plasma concentrations as well as the peak plasma concentrations in all cases. The median tumor: concurrent plasma ratio of idarubicinol was 5.7 (range 1.7–18). The concentration of idarubicinol in the marginal zone between brain and tumor tissue was lower than in central tumor tissue, but was still higher than the plasma concentration in 2 of the 3 examined cases. Bone marrow suppression (platelets CTC grade 2, granulocytes CTC grade 4) occurred after a single dose of 45 ml/m2. No toxicity was seen at a dose of 25 mg/m2. These results, the in vitro activity of idarubicin in glioma, the convenience of oral administration, and its toxicity profile make clinical studies with idarubicin in malignant glioma, and perhaps also in brain metastases from breast cancer worthwhile.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Z¨ulch KJ: Brain Tumors. Their Biology and Pathology. New York, Springer 1986

    Google Scholar 

  2. Berger MS, Leibel SA, Bruner JM: Primary central nervous system tumors of the supratentorial compartment. In: Levin VA, ed. Cancer in the Nervous System Chestchill Livingstone, New York 1996, pp 57–127

  3. Fine HA, Dear KBG, Loeffler JS, Black PM, Canellos GP: Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults. Cancer 71: 2585–2597, 1993

    PubMed  Google Scholar 

  4. Chang CH, Horton J, Schoenfeld D, Salazer O, Peter-Tamayo R, Kramer S, Weinstein A, Nelson JS, Tsukada Y: Comparison of postoperative radiotherapy with combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas. Cancer 52: 997–1007, 1983

    PubMed  Google Scholar 

  5. Brada M, Thomas DGT, Bleehen NM, Roberts JT, Senanayake F, Abram P, Lantos PL, Moss TH, Ironside JW, Whaley JB, Stenning SP: Medical research council (MRC) randomised trial of adjuvant chemotherapy in high grade glioma (HGG). Proc ASCO 17: 400a (abstract), 1998

  6. Mahaley MS: Neuro-oncology index and review: adult primary brain tumors. J Neuro-Oncol 11:85–147, 1991

    Google Scholar 

  7. Posner JB: Neurologic Complication of Cancer. Davis, Philadelphia 1995

  8. Boogerd W, Dalesio O, Bais EM, Van der Sande JJ: Response of brain metastases from breast cancer to systemic chemotherapy. Cancer 69: 972–980, 1992

    PubMed  Google Scholar 

  9. Kristensen CA, Kristjansen PEG, Hansen H: Systemic chemotherapy of brain metastases from small cell lung cancer. J Clin Oncol 10: 1498–1502, 1992

    PubMed  Google Scholar 

  10. Kaaijk P, Troost D, de Boer OJ, Van Amstel P, Bakker PJM, Leenstra S, Bosch DA: Daunorubicin and adriamycin but not BCNU have deleterious effects on organotypic multicellular spheroids of gliomas. Br J Cancer 74: 187–193, 1996

    PubMed  Google Scholar 

  11. Von Holst H, Knochenhamer E, Blomgren H, Collins VP, Ehr L, Lindquist M, Noren G, Peterson C: Uptake of adriamycin in tumour and surrounding brain tissue in patients with malignant gliomas. Acta Neurochir 104: 13–16, 1990

    Google Scholar 

  12. Kuffel MJ, Reid JM, Ames MA: Anthracyclines and their C-13 alcohol metabolites: growth inhibition and DNA damage following incubation with human tumor cells in culture. Cancer Chemoth Pharmacol 30: 51–57, 1992

    Google Scholar 

  13. Reid JM, Pendergrass TW, Krailo MD, Hammond GD, Ames MM: Plasma pharmacokinetics and cerebrospinal fluid concentrations of idarubicin and idarubicinol in pediatric leukemia patients. Cancer Res 50: 6525–6528, 1990

    PubMed  Google Scholar 

  14. Camaggi CM, Strocchi E, Carisi P, Martoni A, Tononi A, Guarraldi M, Benedetti MS, Efthymiopoulos C, Pannuti F: Idarubicin metabolism and pharmacokinetics after intravenous and oral administration in cancer patients: a crossover study. Cancer Chemother Pharmacol 30: 307–316, 1992

    PubMed  Google Scholar 

  15. Beijnen JH, Neef C, Bouma J, Paalman ACA, Underberg WJM: Analysis of 4–demethoxy-daunorubicin and metabolites in plasma and urine. Chem Pharm Bull 36: 3503–3511, 1988

    PubMed  Google Scholar 

  16. Feig SA, Ames MA, Sather HN, Steinherz L, Reid JM, Trigg M, Pendergrass TW, Warkentin P, Gerber M, Leonard M, Bleyer WA, Harris RE: Comparison of idarubicin to daunomycin in a randomized multiding treatment of childhood acute lymphoblastic leukemia at first bone marrow relapse. Med Pediatr Oncol 27: 605–614, 1996

    Google Scholar 

  17. Lopez M, Contegiacomo A, Vici P, Dello-Ioio C, DiLauro L, Pagliarulo C, Carpano S, Giannerelli D, DePlacidio S, Fazio S, Bianco AR: A prospective randomized trial of doxorubicin versus idarubicin in the treatment of advanced breast cancer. Cancer 64: 2431–2436, 1989

    PubMed  Google Scholar 

  18. Martoni A, Plana E, Gueraldi M, Cilenti G, Farris A, Saccani F, Becchi G, Pannuti F: Comparative phase II study of idarubicin versus doxorubicin in advanced breast cancer. Oncology 47: 427–432, 1990

    PubMed  Google Scholar 

  19. Case DC, Hayes DM, Gerber M, Gams R: Phase II study of oral idarubicin in favorable histology non-Hodgkin's lymphoma. Proceed Am Assoc Cancer Res 31: 1146, 1990

    Google Scholar 

  20. Chisesi T, Capnist G, DeDominicis E, Dini E: A phase II study of idarubicin (4–demethoxydaunorubicin) in advanced myeloma. Eur J Cancer Clin Oncol 24: 681–690, 1988

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Slotervaart Hospital, Amsterdam

    W. Boogerd

  2. Department of Neurosurgery, Slotervaart Hospital, Amsterdam

    I.S. Tjahja

  3. Department of Pathology, Slotervaart Hospital, Amsterdam

    M.M. van de Sandt

  4. Department of Pharmacy, Slotervaart Hospital, Amsterdam

    J.H. Beijnen

  5. Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoekhuis, Amsterdam, The Netherlands

    W. Boogerd & J.H. Beijnen

Authors
  1. W. Boogerd
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I.S. Tjahja
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M.M. van de Sandt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J.H. Beijnen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Boogerd, W., Tjahja, I., van de Sandt, M. et al. Penetration of Idarubicin into Malignant Brain Tumor Tissue. J Neurooncol 44, 65–69 (1999). https://doi.org/10.1023/A:1006335517191

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006335517191

Search

Navigation