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Use of AMSA Combination Chemotherapy in Patients with Acute Myelogenous Leukemia Unsuitable for Anthracycline or Mitoxantrone Treatment

  • G. Maschmeyer
  • K. Willborn
  • W. Heit
Conference paper
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 34)

Abstract

Cardiotoxic drugs such as anthracyclines or mitoxantrone are essential components of most established chemotherapy regimens for the treatment of acute myelogenous leukemia (AML). In large multicenter trials, up to 20% of patients <60 years and more than 50% of patients >60 years of age must be primarily excluded from treatment mostly due to their history or clinical signs of congestive heart failure or significant arrhythmias. In addition, many patients with relapsed or refractory disease have been heavily pretreated with anthracyclines and thus are not suitable for further administration of these substances. Studies on this poor-risk subgroup of AML patients are rare and focus on the use of low-dose cytosine arabinoside or other less aggressive drug regimens. Amsacrine has been reported as an effective antileukemic drug from numerous clinical trials since 1980. When administered in a total dose of about 600 mg/m2 in combination with conventional or high-dose cytosine arabinoside, response rates of up to 70% have been observed [1–10]. We therefore conducted a clinical study on the use of amsacrine in combination with cytosine arabinoside for first-line or reinduction chemotherapy in AML patients unsuitable for anthracycline or mitoxantrone treatment.

Keywords

Acute Myeloid Leukemia Clin Oncol Acute Leukemia Acute Myelogenous Leukemia Cytosine Arabinoside 
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.

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References

  1. 1.
    Arlin ZA, Flomenberg N, Gee TS, Kempin SJ, Dellaquila C, Mertelsmann R, Straus DJ, Young CW, Clarkson BD (1981) Treatment of acute leukemia in relapse with 4’-(9-acridinylamino)methanesulfon-m-anisidide ( AMSA) in combination with cytosine arabinoside and thioguanine. Cancer Clin Trials 4: 317–321PubMedGoogle Scholar
  2. 2.
    Arlin ZA, Ahmed T, Mittelman A, Feldman E, Mehta R, Weinstein P, Rieber E, Sullivan P, Baskind P (1987) A new regimen of amsacrine with high-dose cytarabine is safe and effective therapy for acute leukemia. J Clin Oncol 5: 371–375PubMedGoogle Scholar
  3. 3.
    Boccia R, Zighelboim J, Champlin RE, Kim CC, Gale RP (1984) AMSA: a phase II trial in resistant and recurrent acute myelogenous leukemia. Med Pediatr Oncol 12: 178–179PubMedCrossRefGoogle Scholar
  4. 4.
    Dhaliwal HS, Shannon MS, Barnett MJ, Prentice HG, Bragman K, Malpas JS, Lister TA (1986) Treatment of acute leukaemia with m-AMSA in combination with cytosine arabinoside. Cancer Chemother Pharmacol 18: 59–62PubMedCrossRefGoogle Scholar
  5. 5.
    Estey EH, Keating MJ, Smith TL, McCredie KB, Legha SS, Walters RS, Bodey GP, Freireich EJ (1984) Prediction of complete remission in patients with refractory acute leukemia treated with AMSA. J Clin Oncol 2: 102–106PubMedGoogle Scholar
  6. 6.
    Hines JD, Oken MM, Mazza JJ, Keller AM, Streeter RR, Glick JH (1984) High-dose cytosine arabinoside and m-AMSA is effective therapy in relapsed acute nonlymphocytic leukemia. J Clin Oncol 2: 545–549PubMedGoogle Scholar
  7. 7.
    Hines JD, Mazza JJ, Oken MM, Adelstein DJ, Keller A, Bennett JM, O’Connell MJ (1987) Prolonged survival after high-dose cytosine arabinoside and amsacrine induction in patients with previously untreated de novo acute nonlymphocytic leukemia. Semin On-col 14 [Suppl 1]: 37–39Google Scholar
  8. 8.
    Kahn SB, Spiers A, Knospe WH, Soojian M, Glick JH (1987) Amsacrine (4’-(9-acridinylamino)-methanesulfon-m-anisidide) (m-AMSA) and 5-azacytidine ( AZA) for remission induction in patients with relapsed adult acute nonlymphocytic leukemia. Am J Clin Oncol 10: 78–81PubMedCrossRefGoogle Scholar
  9. 9.
    Legha SS, Keating MJ, McCredie KB, Bodey GP, Freireich EJ (1982) Evaluation of AMSA in previously treated patients with acute leukemia: results of therapy in 109 adults. Blood 60: 484–490PubMedGoogle Scholar
  10. 10.
    Zittoun R, Bury J, Stryckmans P, Löwenberg B, Rozendaal KY, Haanen C, Kerkhofs M, Jehn U, Willemze R (1985) Amsacrine with high-dose cytarabine in acute leukemia. Cancer Treat Rep 69: 1447–1448PubMedGoogle Scholar
  11. 11.
    Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, Sultan C (1976) Proposals for the classification of the acute leukaemias: French-American-British (FAB) Co-operative Group. Br J Haematol 33: 451–458PubMedCrossRefGoogle Scholar
  12. 12.
    Hiddemann W, Kreutzmann H, Straif K, Ludwig WD, Mertelsmann R, DonhuijsenAnt R, Lengfelder E, Arlin Z, Büchner T (1987) High-dose cytosine arabinoside and mitoxantrone: a highly effective regimen in refractory acute myeloid leukemia. Blood 69: 744–749PubMedGoogle Scholar
  13. 13.
    Mufti GJ, Oscier DG, Hamblin TJ, Bell AJ (1983) Low doses of cytarabine in the treatment of myelodysplastic syndrome and acute myeloid leukemia. N Engl J Med 309: 1653–1654PubMedCrossRefGoogle Scholar
  14. 14.
    Winter JN,Variakojis D, Gaynor ER, Larson RA, Miller KB (1985) Low-dose cytosine arabinoside (ara-C) therapy in the myelodysplastic syndromes and acute leukemia. Cancer 56: 443–449PubMedCrossRefGoogle Scholar
  15. 15.
    Wiernik PH, Serpick AA (1970) Factors affecting remission and survival in adult acute nonlymphocytic leukemia (ANLL). Medicine 49: 505–513PubMedCrossRefGoogle Scholar
  16. 16.
    Louie AC, Issell BF (1985) Amsacrine ( AMSA) — a clinical review. J Clin Oncol 3: 562–593PubMedGoogle Scholar
  17. 17.
    Weiss RB, Grillo-Lopez AJ, Marsoni S, Posada JG Jr, Hess F, Ross BJ (1986) Amsacrine-associated cardiotoxicity: an analysis of 82 cases. J Clin Oncol 4: 918–928PubMedGoogle Scholar
  18. 18.
    Mittelman A, Arlin ZA (1983) AMSAinduced seizures in patients with hypokalemia. Cancer Treat Rep 67: 102–103PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • G. Maschmeyer
    • 1
  • K. Willborn
    • 1
  • W. Heit
    • 1
  1. 1.Department of Hematology and OncologyEvangelic Hospital, Essen-WerdenEssen 16Germany

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