Advertisement

Oral Idarubicin in Pretreated Pediatric Acute Leukemia

  • S. Bielack
  • U. Bode
  • M. Goebel
  • P. Gutjahr
  • R. Haas
  • N. Kuhn
  • H. Siewert
  • R. Erttmann
Conference paper
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 34)

Abstract

Anthracyclines are among the most useful drugs in the treatment of both lymphoblastic (ALL) and nonlymphoblastic (ANLL) acute leukemias of childhood. However, the benefit of the most commonly used anthracyclines daunorubicin and doxorubicin is limited by their cardiotoxicity [1] and by resistance against these compounds. The daunorubicin analog idarubicin (4-demethoxydaunorubicin) might be less cardiotoxic and has shown greater antileukemic efficacy in some preclinical and clinical trials [2]. In addition, the chemical structure of idarubicin leads to appreciable resorption of active drug after oral application [3, 4], allowing therapy in an outpatient setting. We therefore conducted an open, multicenter trial assessing the toxicity and efficacy of oral idarubicin in refractory acute leukemia in children.

Keywords

Maximum Tolerate Dose Acute Leukemia Antileukemic Activity Oral Idarubicin Refractory Acute Leukemia 
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.
    Von Hoff DD, Rosencweig M, Piccart M (1980) The cardiotoxicity of anticancer agents. Semin Oncol 9: 23Google Scholar
  2. 2.
    Carella AM, Berman E, Maraone M, Ganzi-na F (1990) Idarubicin in the treatment of acute leukemias. An overview of preclinical and clinical studies. Haematologica (Pavia) 75: 1–11Google Scholar
  3. 3.
    Smith DB, Margison JM, Lucas SB, Wilkinson PM, Howell A (1987) Clinical pharmacology of oral and intravenous 4-demethox-ydaunorubicin. Cancer Chemother Pharmacol 19: 138–142PubMedCrossRefGoogle Scholar
  4. 4.
    Gillies HC, Herriot D, Liang R, Ohashi K, Rogers HJ, Harper PG (1987) Pharmacokinetics of idarubicin (4-demethoxydaunorubi-cin; IMI-30; NSC 256439) following intravenous and oral administration in patients with advanced cancer. Br J Clin Pharmacol 23: 303–310PubMedGoogle Scholar
  5. 5.
    Wiernik P (ed) (1989) Idarubicin: a new presence in leukemias. Semin Oncol 16 [Suppl 2]: 1–36Google Scholar
  6. 6.
    Casazza AM, Pratesi G, Giuliani F, DiMarco A (1980) Antileukemic activity of 4-deme-thoxydaunorubicin in mice. Tumori 66: 549–552PubMedGoogle Scholar
  7. 7.
    Erttmann R, Bode U, Erb N, Forcadell de Dios P, Gutjahr P, Haas R, Kuhn N, Siewert H, Landbeck G (1988) Antineoplastische Wirksamkeit und Toxizität von Idarubicin (4-Demethoxydaunorubicin) bei rezidivierten akuten Leukämien des Kindesalters. Klin Pädiatr 200: 200–204PubMedCrossRefGoogle Scholar
  8. 8.
    Daghestani AN, Arlin ZA, Leyland-Jones B, Gee TS, Kempin SJ, Mertelsmann R, Budman D, Schulman P, Baratz R, Williams L, Clarkson BD, Young CW (1985) Phase I and II clinical and pharmacological study of 4-demethoxydaunorubicin (idarubicin) in adult patients with acute leukemia. Cancer Res 45: 1408–1412PubMedGoogle Scholar
  9. 9.
    Carella AM, Santini G, Martinengo M, et al. (1985) 4-Demethoxydaunorubicin in refractory or relapsed acute leukemias. A pilot study. Cancer 55 1452–1454Google Scholar
  10. 10.
    Harrousseau JL, Hurteloup P, Reiffers J, et al. (1987) Idarubicin in the treatment of relapsed or refractory acute myeloid leukemia. Cancer Treat Rep 71: 991–995Google Scholar
  11. 11.
    Tan CTC, Hancock C, Steinherz P, Bacha DM, Steinherz L, Luks E,Winick N, Meyers P, Mondora A, Dantis E, Niedzwiecki D, Stevens YW (1987) Phase I and clinical pharmacological study of 4-demethoxydau-norubicin (idarubicin) in children with advanced cancer. Cancer Res 47: 2990–2995PubMedGoogle Scholar
  12. 12.
    Madon E, Grazia G, De Bernardi B, Comelli A, Carli M, Sainati L, Paolucci G, Canino R, Colella R, Bagnulo S, Di Pietro N (1987) Phase II study of idarubicin administered iv to pediatric patients with acute lymphoblastic leukemia. Cancer Treat Rep 71: 855–856PubMedGoogle Scholar
  13. 13.
    Harris R, Feig S, Baum E, Holcenberg J, Pendergrass T, Bleyer A, Holt C, Krailo M, Hammond D (1988) Idarubicin ( IDR) vs daunomycin for reinduction of relapsed childhood ALL - a CCSG study. Proc Am Soc Clin Oncol 7: 189Google Scholar
  14. 14.
    Tan C, Bacha D, Hancock C (1984) New anthracyclines in childhood cancer. 14th International Congress of Chemotherapy, (abstr No 104)Google Scholar
  15. 15.
    Pui CH, de Graaf SS, Dow LW, Rodman JH, Evans WE, Alpert BS, Murphy SB (1988) Phase I clinical trial of orally administered 4-demethoxydaunorubicin (idarubicin) with pharmacokinetic and in vitro drug sensitivity testing in children with refractory leukemia. Cancer Res 48: 5348–5352Google Scholar
  16. 16.
    Lowenthal RM (1987) A possible special role for oral idarubicin in the treatment of leukemia following myelodysplastic syndrome. In: Mandelli F, Polli E, Clarkson B (eds) Proceedings of the session in idarubicin in the treatment of acute leukemia. 4th International Symposium on Therapy of Acute Leukemia. Excerpta Medica, Amsterdam, pp 50–55Google Scholar
  17. 17.
    Höchster H, Green M, Liebes L, Speyer JL, Wernz J, Blum R, Muggia F (1990) Good tolerance of weekly oral idarubicin: a phase I study with pharmacology. Cancer Chemother Pharmacol 26: 297–300PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • S. Bielack
    • 1
  • U. Bode
    • 2
  • M. Goebel
    • 3
  • P. Gutjahr
    • 4
  • R. Haas
    • 5
  • N. Kuhn
    • 6
  • H. Siewert
    • 7
  • R. Erttmann
    • 1
  1. 1.Abteilung für pädiatrische Hämatologie und OnkologieUniversitätskinderklinikGermany
  2. 2.UniversitätskinderklinikBonnGermany
  3. 3.Farmitalia Carlo Erba GmbHFreiburgGermany
  4. 4.UniversitätskinderklinikMainzGermany
  5. 5.UniversitätskinderklinikMünchenGermany
  6. 6.Kinderklinik Wuppertal, Klinikum BarmenWuppertalGermany
  7. 7.Universitätskinderklinik RWTHAachenGermany

Personalised recommendations