Annals of Hematology

, Volume 71, Issue 1, pp 35–39

Mitoxantrone and cytosine arabinoside as treatment for acute myeloblastic leukemia in older patients

  • P. K. MacCallum
  • A. Z. S. Rohatiner
  • C. L. Davis
  • J. S. Whelan
  • A. M. Oza
  • J. Lim
  • S. Love
  • J. A. L. Amess
  • M. Leahy
  • R. K. Gupta
  • C. G. A. Price
  • T. A. Lister
Original Article

Abstract

The majority of patients with acute myeloid leukemia (AML) are elderly, and their response to chemotherapy is poorer than that of younger patients. The combination of mitoxantrone (MTN) and cytosine arabinoside (Ara-C) is a possible alternative to an anthracycline/Ara-C combination for the treatment of AML in these patients. Of 52 older patients (> 59 years) referred over a 3.5-year period, 33 patients (age range 60–78 years, median 67 years) received MTN and Ara-C as therapy for newly diagnosed AML. MTN was administered at a dose of 12 mg/m2/day, intravenously, for 3 days (23 patients), or 10 mg/m2/day for 5 days (10 patients), and Ara-C at a dose of 100 mg/m2 twice daily, intravenously, for 7 days. Complete remission (CR) was achieved in 16/33 patients (48%). The median remission duration was 6 months (range 1–37 months). The median survival was 14 months for those who achieved CR compared with 9 months for those with resistant disease. Two patients remain in first CR after 13 and 37 months, but three patients died whilst receiving consolidation therapy. In selected elderly patients with AML, the combination of MTN and Ara-C provides an acceptable alternative to an anthracycline/ Ara-C regimen, with a higher CR rate than historical controls. However, the CR rate and remission duration remain low compared with those of younger patients, supporting the need to investigate new approaches to treatment in this population.

Key words

Acute myeloid leukemia Cytosine arabinoside Elderly Mitoxantrone 

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References

  1. 1.
    Arlin Z, Case DC, Moore J et al. (1990) Randomized multicentre trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocyctic leukemia (ANLL). Leukemia 4:177–183PubMedGoogle Scholar
  2. 2.
    Beguin Y, Bury J, Fillet G et al. (1985) Treatment of acute nonlymphocytic leukemia in young and elderly patients. Cancer 56:2587–2592PubMedGoogle Scholar
  3. 3.
    Bennett JM, Catovsky D, Daniel M-T et al. (1976) Proposals for the classification of the acute leukaemias. Br J Haematol 33:451–458PubMedGoogle Scholar
  4. 4.
    Bennett JM, Catovsky D, Daniel MT et al. (1983) Proposed revised criteria for the classification of acute myeloid leukemia. Ann Intern Med 105:620–625Google Scholar
  5. 5.
    Brito-Babapulle F, Catovsky D, Galton DAG (1987) Clinical and laboratory features of de novo acute myeloid leukaemia with trilineage myelodysplasia. Br J Haematol 66:445–450PubMedGoogle Scholar
  6. 6.
    Buchner T, Hiddemann W, Koenigsmann M et al. (1991) Recombinant human granulocyte-macrophage-colony-stimulating factor after chemotherapy in patients with acute myeloid leukemia at higher age or after relapse. Blood 78:1190–1197PubMedGoogle Scholar
  7. 7.
    Cancer Statistics Registrations (1986) O.P.C.S. Her Majesty's Stationary OfficeGoogle Scholar
  8. 8.
    Cox DR (1972) Regression models and life tables. J R Statist Soc (B) 34:187–220Google Scholar
  9. 9.
    Estey EH, Keating MJ, McCredie KB et al. (1982) Causes of initial remission induction failure in acute myelogenous leukemia. Blood 60:309–315PubMedGoogle Scholar
  10. 10.
    Estienne MH, Fenaux P, Preudhomme C et al. (1990) Prognostic value of dysmyelopoietic features in de novo acute myeloid leukaemia:a report on 132 patients. Clin Lab Haematol 12:57–65PubMedGoogle Scholar
  11. 11.
    Fialkow PJ, Singer JW, Raskind WH et al. (1987) Clonal development, stem-cell differentiation, and clinical remissions in acute nonlymphocytic leukemia. N Engl J Med 317:468–473PubMedGoogle Scholar
  12. 12.
    Foon KA, Zighelboim J, Yale C et al. (1981) Intensive chemotherapy is the treatment of choice for elderly patients with acute myelogenous leukemia. Blood 58:467–470PubMedGoogle Scholar
  13. 13.
    Kahn SB, Begg CB, Mazza JJ (1984) Full dose versus attenuated dose daunorubicin, cytosine arabinoside and 6-thioguanine in the treatment of acute non-lymphocytic leukemia in the elderly. J Clin Oncol 2:865–870PubMedGoogle Scholar
  14. 14.
    Keating MJ, McCredie KB, Benjamin RS et al. (1981) Treatment of patients over 50 years of age with acute myelogenous leukemia with a combination of rubidazone and cytosine arabinoside, vincristine, and prednisolone (ROAP). Blood 58:584–591PubMedGoogle Scholar
  15. 15.
    Keating MJ, Smith TL, Gehan EA et al. (1982) A prognostic factor analysis for use in development of predicitive models for response in adult acute leukemia. Cancer 50:457–465PubMedGoogle Scholar
  16. 16.
    Liu Yin JA, Johnson PRE, Davies JM et al. (1991) Mitozantrone and cytosine arabinoside as first-line therapy in elderly patients with acute myeloid leukaemia. Br J Haematol 79:415–420PubMedGoogle Scholar
  17. 17.
    Lowenberg B, Zittoun R, Kerkhofs H et al. (1989) On the value of intensive remission induction chemotherapy in elderly patients of 65+ years with acute myeloid leukemia: a randomized phase-III study of the European Organization for Research and Treatment of Cancer Leukemia Group. J Clin Oncol 7:1268–1274PubMedGoogle Scholar
  18. 18.
    Mayer RJ, Davis RB, Schiffer CA et al. (1994) Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med 331:896–903PubMedGoogle Scholar
  19. 19.
    Peto R, Pike MC, Armitage P et al. (1977) Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. Br J Cancer 35:1–39PubMedGoogle Scholar
  20. 20.
    Rai KR, Holland JF, Glidewell OJ et al. (1981) Treatment of acute myelocytic leukemia: a study by Cancer and Leukemia Group B. Blood 58:1203–1212PubMedGoogle Scholar
  21. 21.
    Rees JKH, Gray RG, Swirsky D et al. (1986) Principal results of the Medical Research Council's 8th acute myeloid leukaemia trial. Lancet 2:1236–1241PubMedGoogle Scholar
  22. 22.
    Resegotti L (1992) Treatment of acute nonlymphoid leukemia (ANLL) in elderly patients. The GIMEMA experience. Leukemia 6 [Suppl 2]:72–75PubMedGoogle Scholar
  23. 23.
    Rohatiner AZS, Lister TA (1990) The treatment of acute myelogenous leukemia. In: Henderson ES, Lister TA (eds) Leukemia. WB Saunders, Philadelphia, pp 485–513Google Scholar
  24. 24.
    Shepherd JD, Reece DE, Barnett MJ et al. (1993) Induction therapy for acute myelogenous leukemia in patients over 60 years with intermediate-dose cytosine arabinoside, mitoxantrone and etoposide. Leuk Lymph 9:211–215Google Scholar
  25. 25.
    Smith TL, Gehan EA, Keating MJ et al. (1982) Prediction of remission in adult acute leukemia: development and testing of predictive models. Cancer 50:466–472PubMedGoogle Scholar
  26. 26.
    Swirsky DM, De Bastos M, Parish SE et al. (1986) Features affecting outcome during remission induction of acute myeloid leukaemia in 619 adult patients. Br J Haematol 64:435–453PubMedGoogle Scholar
  27. 27.
    Tilly H, Castaigne S, Bordessoule D et al. (1990) Low-dose cytarabine versus intensive chemotherapy in the treatment of acute nonlymphocytic leukemia in the elderly. J Clin Oncol 8:272–279PubMedGoogle Scholar
  28. 28.
    Tucker J, Thomas A, Gregory WM et al. (1990) Acute myeloid leukemia in elderly adults. Hematol Oncol 8:13–21PubMedGoogle Scholar
  29. 29.
    Yates J, Glidewell O, Wiernik P et al. (1982) Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study. Blood 60:454–462PubMedGoogle Scholar
  30. 30.
    Zittoun R, Cadiou M, Bayle C et al. (1984) Prognostic value of cytologic parameters in acute myelogenous leukemia. Cancer 53:1526–1532PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • P. K. MacCallum
    • 1
  • A. Z. S. Rohatiner
    • 2
  • C. L. Davis
    • 2
  • J. S. Whelan
    • 2
  • A. M. Oza
    • 2
  • J. Lim
    • 2
  • S. Love
    • 3
  • J. A. L. Amess
    • 1
  • M. Leahy
    • 1
  • R. K. Gupta
    • 2
  • C. G. A. Price
    • 2
  • T. A. Lister
    • 2
  1. 1.Department of HematologySt. Bartholomew's HospitalWest Smithfield, LondonUK
  2. 2.ICRF Department of Medical OncologySt. Bartholomew's HospitalLondonUK
  3. 3.Medical Statistics LaboratoryImperial Cancer Research FundLondonUK

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