Abstract
Nineteen patients with relapsed or refractory acute myelogenous leukemia were treated with escalating doses of aclacinomycin (ACLA 20–30 mg/m2 daily for 5 days) and intermediate-dose cytosine arabinoside (Ara-C 1 g/m2 twice daily for 4 days). Most patients had received previous therapy with high- or intermediate-dose Ara-C plus mitoxantrone (HAM, IAM) and TAD (6-thioguanine, standard-dose cytosine arabinoside, and daunorubicin). Four patients had had repeated relapses and another three were treated for primary treatment failure following induction with HAM or I AM.
Twelve patients (63%) responded: nine (47%) entered complete remission (CR) and three (16%) had a partial remission. None of the patients refractory to HAM or IAM went into CR. Side effects from this treatment were generally mild. However, urinary tract toxicity with hematuria and dysuria turned out to be dose limiting, since all patients receiving ACLA 30 mg/m2 experienced grade 2–3 toxicity (WHO). These side effects were mild when ACLA was used at 20 mg/m2 (grade 1–2 toxicity only, in 21% of patients). Consequently, the study was continued with a fixed ACLA dose of 20 mg/m2 that was found to be safe and well tolerated. The overall CR rate of 47% compares well with other salvage protocols and ACLA combinations, arguing for further evaluation of this therapeutic approach.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Glucksberg H, Buckner CD, Fefer A, DeMarsh Q, Copleman D, Dobrow RB, Huff J, Kjobech C, Hill AS, Dittmann W, Neimann PE, Cheever MA, Einstein AB Jr, Thomas ED (1975) Combination chemotherapy for acute nonlymphoblastic leukemia in adults. Cancer Chemother Rep 59: 1131–1137
Preisler HD, Rustum Y, Henderson ES, Bjornsson S, Creaven PJ, Higby DJ, Freemann A, Gailani S, Naeher C (1979) Treatment of acute nonlymphocytic leukemia: use of anthracyclin-cytosine arabinoside induction therapy and comparison of two maintenance regimens. Blood 53: 455–464
Büchner T, Urbanitz D, Hiddemann W, Rühl H, Ludwig WD, Fischer J, Aul HC, Vaupel HA, Kuse R, Zeile G, Nowrousian MR, König HJ, Walter M, Wendt FC, Sodomann H, Hossfeld DK, Paleske von A, Löffler H, Gassmann W, Hellriegel K-P, Fülle HH, Lunscken CH, Emmerich B, Pralle H, Pees HW, Pfeundschuh M, Bartels H, Poeppen K-M, Schwerdtfeger R, Donhuijsen-Ant R, Mainzer K, Bonfert B, Köppler H, Zurborn K-H, Ranft K, Thiel E, Heinecke A (1985) Intensified induction and consolidation with or without maintenance chemotherapy for acute myeloid leukemia (AML). Two multicenter studies of the German AML Cooperative Group. J Clin Oncol 3: 1583–1589
Gale RP, Foon KA (1987) Therapy of acute myelogenous leukemia. Sem Hematology 24: 40–54
Willemze R, Zwaan FE, Colpin G, Keuning JJ (1982) High dose cytosine arabinoside in the management of refractory acute leukemia. Scand J Haematol 29: 141
Hiddemann W, Büchner Th, van de Loo J (1989) Grundlagen der Rezidivtherapie bei akuter myeloischer Leukämie. Dtsch Med Wochenschr 114: 599 - 605
Warrel RP Jr (1986) Aclacinomycin A: clinical development of a novel anthracycline antibiotic in the haematological cancers. Drugs Exp Clin Res 12: 275–282
Yamada K, Nakamura T, Tsuruo T, Kitnara T, Maekawa T, Oasaka Y, Kurita S, Masaoka T, Takaku F, Hirota Y, Amaki I, Osamura S, Ito M, Nakano N, Ogyro M, Inagaki J, Onozawa K (1980) A phase II study of aclacinomycin A in acute leukemia in adults. Cancer Treat Rev 7: 177–182
Bouhour JB, Delajarte AY, Chiffoleau S, Fumuleau P, Nicolas G (1983) Comparison of the cardiotoxicity of adriamycin and aclacinomycin A in the heart. Optical and electron microscopic study. Arch Mal Coeur 76: 1270–1274
Rowe JM, Chang AYC, Bennet JM (1988) Aclacinomycin A and etoposide (VP-16- 213): an effective regimen in previously treated patients with refractory acute myelogenous leukemia. Blood 71: 992–996
Mitrou PS, Kuse R, Anger H, Herrmann R, Bonfert B, Pralle H, Thiel E, Westerhausen M, Mainzer K, Bartels H (1985) Aclarubicin ( Aclacinomycin-A) in the treatment of relapsing acute leukemias. Eur J Cancer 21: 919–923
Willemze R, Fibbe WE, Zwaan FE (1983) Experience with intermediate and high-dose cytosine arabinoside in relapsed and refractory acute leukemia. Neth J Med 26: 215–219
Herzig RG, Wolff SN, Lazarus HM, Phillips GL, Karanes C, Herzig GP (1983) High-dose cytosine arabinoside therapy for refractory leukemia. Blood 62: 361–369
Petersen-Bjergaard J, Brincker H, Ellegaard J, Drivsholm A, Freund L (1984) Phase II trial of aclacinomycin-A in acute non-lymphocytic leukemia refractory to treatment with daunorubicin. Proc Am Soc Clin Oncol 3: 208
Warrell RP Jr, Arlin ZA, Kempin SJ, Young CW (1982) Phase I-II evaluation of a new anthracycline antibiotic, aclacinomacin A, in adults with refractory leukemia. Cancer Treat Rep 66: 1619–1623
Holowiecki J, Lutz D (1987) The current status of Aclarubicin in the combination chemotherapy of untreated and relapsed or resistant ANLL — a multicenter study. BICON Symposium, Munich, 1987
Hansen OP, Ellegaard J, Madsen PB, Brincker H, Christensen BE, Killmann SAa, Laursen ML, Karle H, Drivsholm Aa, Jensen MK, Laursen B, Jans H, Hippe E, Petersen-Bjergaard, Nissen N, Thorling K, Jensen KB (1988) Combination chemotherapy with Aclarubicin (ACR) plus cytosine arabinoside (CA) versus daunorubicin (DNR) plus cytosine arabinoside in de novo acute myelocytic leukemia (AML): a Danish national trial. Am Soc Clin Oncol Proc 7–675
Hines JD, Oken MM, Mazza JJ, Keller AM, Streeter RR, Glick JH (1984) High- dose cytosine arabinoside and m-AMSA is effective therapy in replapsed acute non- lymphocytic leukemia. J Clin Oncol 2: 545 - 549
Paciucci PA, Ohnuma T, Cuttner J, Silver RT, Holland JF (1983) Mitoxantrone in patients with acute leukemia in relapse. Cancer Res 43: 3919–3922
Keating MJ, Kanterjian H, Smith TL, Estey E, Walters R, Andersson B, Beran M, McCredie KB, Freireich EJ (1989) Response to salvage therapy and survival after relapse in acute myelogenous leukemia. J Clin Oncol 7: 1071–1080
Dabich L, Bull FE, Beltran G, Athens JW, Coltman CA Jr, Weick JK, Van Slyck EJ, Amare M (1986) Phase II evaluation of aclarubicin in refractory adult acute leukemia: a Southwest Oncology Group Study. Cancer Treat Rep 70: 967–969
Sampi K, Sakurai M, Kaneka Y, Hattori M (1986) Aclacinomycin A and behenoyl arabinofuranosylcytosine combination chemotherapy for previously untreated acute leukemia. Oncology 43: 18–22
Machover D, Gastiaburu J, Delgado M, Goldschmidt E, Hulhoven R, Misset JL, de Vassal F, Tapiero H, Ribaud P, Schwarzenberg L (1984) Phase I-II study of aclarubicin for treatment of acute myeloid leukemia. Cancer Treat Rep 68: 881–886
Amadori S, Papa G, Avvisati G, Fenu S, Monarca B, Petu MC, Pulsoni A, Mandelli F (1984) Sequential combination of high-dose ARA-C (Hi DAC) and asparaginase ( ASP) for the treatment of advanced acute leukemia and lymphoma. Leuk Res 8: 729–735
Decker RW, Ho WG, Champlin RE (1987) Phase II study of amsacrine and high-dose cytarabine for resistant acute myelogenous leukemia. Cancer Treat Rep 71: 881–882
Hiddemann W, Kreutzmann H, Straif K, Ludwig W-D, Mertelsmann R, Planker M, Donhuijsen-Ant R, Lengfelder E, Arlin Z, Büchner T (1987) High-dose cytosine arabinoside in combination with mitoxantrone for the treatment of refractory acute myeloid and lymphoblastic leukemia. Semin Oncol 14: 73–77
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1990 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Lindemann, A. et al. (1990). Low-Dose Aclacinomycin and Intermediate-Dose Cytosine Arabinoside in Relapsed and Refractory Acute Myelogenous Leukemia. In: Hiddemann, W., Mertelsmann, R. (eds) New Findings on Aclarubicin in the Treatment of Acute Myeloid Leukemia. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-75720-4_2
Download citation
DOI: https://doi.org/10.1007/978-3-642-75720-4_2
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-52613-1
Online ISBN: 978-3-642-75720-4
eBook Packages: Springer Book Archive