Summary
A combination of two interacalating agents, mitoxantrone and daunorubicin with vincristine (the DON regimen) was studied in 16 patients with refractory acute leukemia, including three patients with myeloblastic transformation of refractory anemia with excess of myeloblasts after the failure of first-line chemotherapy and one additional patient with AML relapsing while off therapy. All patients had been heavily pretreated prior to receiving the DON regimen, and all but two had previously received high-dose anthracyclines. Of the 17 patients, nine (53%) who achieved complete remissions (CR) had myeloblastic leukemia. The three patients with acute lymphocytic leukemia did not achieve CR. Cardiac toxicity occurred in two patients and contributed to death in one. These results in very poor risk leukemia suggest a possible synergism in the action of the two intercalating agents and absence of increased cardiotoxicity.
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Arlin ZA, Dukart G, Schock I, Resiman A, Moore J, Silver RA, Cassileth P, Bertino J, Gams R, Lederle Cooperative Group (1985a) Phase I–II trial of mitoxantrone in acute leukemia: an interim report. Invest New Drugs 3: 213
Arlin ZA, Gaddipati J, Ahmed T, Mittelman A, Friedland M, Rieber E (1985b) Treatment of acute leukemia with AMSA-CRINE and high dose cytarabine. Cancer Treat Rep 69: 1001
Bernasconi C, Lazzarino M, Bezwoda NR, De Bock R, Hutchinson R, Mandelli F, Windfield DA (1987) Mitoxantrone as single agent in refractory acute leukemia: a multiinstitutional study. Abstract 121, 4th International Symposium on Therapy of Acute Leukemias, Rome, 7–12 February
Capizzi RL, Davis R, Powell B, Cuttner J, Ellison RR, Cooper MR, Dillman R, Major WB, Dupre E, McIntyre OR (1987) Synergy between high dose aracytine and Asparaginase in adults with refractory and relapsed acute myelogenous leukemia. Abstract 347, 4th International Symposium on Therapy of Acute Leukemias, Rome, 7–12 February
Durr FE (1984) Biologic and biochemical effects of mitoxantrone. Semin Oncol 11 (3) [Suppl. 1]:3
Durr FE, Wallace RE, Citarella RV (1983), Molecular and biochemical pharmacology of mitoxantrone. Cancer Treat Rev 10 [Suppl. B]:3
Dutcher JP, Pacciuci PA, Wiernick PH, Strauman JJ, Cuttner J, Holland JF (1987) Mitoxantrone + ARAC in the treatment of relapsed or refractory ANLL. Abstract 126, 4th International Symposium on Therapy of Acute Leukemias, Rome, 7–12 February
Foye WO, Vajragupta OPA, Sengupta SK (1982) DNA binding specificity and RNA polymerase inhibitory activity of bis (aminoalkyl) anthraquinones and bis (methylthio) vinylquinone iodides. J Pharm Sci 71: 253
Gale RP, Foon KA (1986) Acute myeloid leukemia: recent advances in therapy. Clin Hematol 15 (3): 781
Herzig RH, Lazarus HM, Wolff SN, Phillips GL, Herzig GP (1985) High dose cytosine arabinoside therapy with and without anthracycline antibiotics for remission reinduction of acute non lymphoblastic leukemia. J Clin Oncol 3: 992
Hiddeman W, Kreutzmann H, Straif K, Ludwig WD, Donhuytsen-Ant R, Engfelder E, Arlin Z, Buchner T (1986) High dose cytosine-arabinoside and mitoxantrone in refractory acute myeloid leukemia: a clinical phase I/II study. Onkologie 9: 144
Hiddemann W, Kreutzmann H, Straig K, Ludwig WD, Mertelsmann R, Donhuijsen-Ant R, Lengenfelder E, Arlin Z, Buchner T (1987) High dose cytosine arabinoside and mitoxantrone therapy of refractory acute myeloid leukemia. Abstract 125, 4th International Symposium on Therapy of Acute Leukemias, Rome, Feburary 7–12
Hines JD, Oken MM, Mazza J, Keller AM, Streeter RR, Glick JH (1984) High dose cytosine arabinoside and M-AMSA is effective therapy in relapsed acute non lymphoblastic leukemia. J Clin Oncol 2: 545
Ho AD, Lipp T, Ehninger G, Meyer P, Freund M, Hunstein W (1986) Combination therapy with mitoxantrone and etoposide in refractory acute myelogenous leukemia. Cancer Treat Rep 70: 1025
Mertelsmann R, Thaler HT, To L, Gee TS, McKenzie Sue, Schauer P, Friedman A, Arlin ZA, Cirrinclon C, Clarkson B (1980) Morphological classification response to therapy and survival in 263 adult patients with acute non lymphoblastic leukemia. Blood 56: 773
Meyer P, Ho AD, Ehninger G, Mjaaland I, Heidemann E, Seither E (1985) Mitoxantrone in the treatment of relapsed and refractory acute leukemia. Invest New Drugs 3: 203
Mimnaugh EG, Trush MA, Ginsburg E, Gram TE (1982) Differential effects of anthracycline drugs on rat heart and liver microsomal reduced nicotinamide adenine dinucleotide phosphate-dependent lipid peroxidation. Cancer Res 42: 3574
Moore JO, Olsen GA (1984) Novantrone in the treatment of refractory acute leukemia. In: New perspectives in chemotherapy: focus on novantrone. Toronto, p 19
Paciucci PA (1987) Combination chemotherapy with mitoxantrone: The Mount Sinaï studies. Abstract 120, 4th International Symposium on Therapy of Acute Leukemias. Rome, 7–12 February
Starling KA, Hulne AF, Vats TS, Schock I, Dukart G (1985) Mitoxantrone in refractory acute leukemia in children: A phase I study. Invest New Drugs 3: 191
Wallace RE, Murdock KC, Angier RB, Durr FE (1979) Activity of a novel anthracenedion, 1,4-Dihydroxy-5,8-bis[(2-(2-Rydroxyethyl) amino)]-9,10 anthracendione dihydrochloride, against experimental tumors in mice. Cancer Res 39: 1570
Willemze R, Zwaan FE, Coplin G, Kenning JJ (1982) Highdose cytosine arabinoside in relapsed acute non-lymphocytic leukemia. Br J Haematol 50: 699 (Abstr)
Yates J, Glidewell O, Wiernik P, Cooper MR, Steinberg D, Dosik H, Levy R, Hoagland C, Henry P, Gottlieb A, Cornell C, Berenberg J, Hutchison JL, Raich P, Nissen N, Ellison RR, Frelick R, Watson JG, Falkson G, Silver RT, Ohaurani F, Green M, Henderson E, Leone L, Hollands JF (1982) Cytosine-arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia. CAL 6b study. Blood 60: 454
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Laporte, J.P., Gorin, N.C., Lemonnier, M.P. et al. A new combination of two intercalating agents (mitoxantrone + daunomycin) in adult refractory acute leukemia: the DON protocol. Cancer Chemother. Pharmacol. 22, 344–346 (1988). https://doi.org/10.1007/BF00254243
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DOI: https://doi.org/10.1007/BF00254243