Low-Dose Aclacinomycin and Intermediate-Dose Cytosine Arabinoside in Relapsed and Refractory Acute Myelogenous Leukemia
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.
KeywordsToxicity Leukemia Lipase Etoposide Vincristine
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- 3.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: 1583–1589Google Scholar
- 4.Gale RP, Foon KA (1987) Therapy of acute myelogenous leukemia. Sem Hematology 24: 40–54Google Scholar
- 6.Hiddemann W, Büchner Th, van de Loo J (1989) Grundlagen der Rezidivtherapie bei akuter myeloischer Leukämie. Dtsch Med Wochenschr 114: 599 - 605Google Scholar
- 7.Warrel RP Jr (1986) Aclacinomycin A: clinical development of a novel anthracycline antibiotic in the haematological cancers. Drugs Exp Clin Res 12: 275–282Google Scholar
- 9.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: 1270–1274Google Scholar
- 11.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: 919–923Google Scholar
- 14.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: 208Google Scholar
- 16.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, 1987Google Scholar
- 17.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 7–675Google Scholar
- 24.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: 729–735Google Scholar
- 26.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: 73–77PubMedGoogle Scholar