TITLE: Cytosine arabinoside (NSC-63878) and daunorubicin (NSC-83142) therapy in acute nonlymphocytic leukemia
AUTHORS: Yates JW, Wallace HJ Jr, Ellison RR, Holland JF
JOURNAL: Cancer Chemother Rep. 1973;57(4):485-8. PMID: 4586956
Nowadays, the majority of patients with acute myeloid leukemia (AML) achieve a complete remission and many are cured. This remarkable achievement takes place with a standardized induction regimen consisting of an anthracycline and cytarabine. The landmark paper in 1973 – from the prestigious USA group of James Holland at the Roswell Park Memorial Institute in Buffalo, New York – reported on an astounding complete remission rate of 63% among patients with both previously-treated and previouslyuntreated AML. The drugs used were the anthracycline, daunorubicin (formerly rubidomycin in France and daunomycin in the USA), and the pyrimidine antimetabolite, cytosine arabinoside. For a decade prior to this work, each of these drugs was shown to have potent anti-leukemic activity as single agents1,2 and even combinations of these two drugs had been reported.3 In all cases only a small number of remissions were achieved and they were of very short duration. The ultimate breakthrough came, not with the addition of new drugs, but after longer exposure of the leukemic cells to the combination of daunorubicin and cytarabine, as cytosine arabinoside is now known. This breakthrough combination and schedule of drugs for AML, widely known as the “7 and 3” regimen, dramatically changed the prognosis of patients, has remained the backbone of standard therapy for close to five decades, and, amazingly, is still going strong. This remarkable development has been at the core of the current constantly improving outlook for newly-diagnosed patients with AML. From having an incurable disease in the early 1970s, approximately 35-40% of young adults can now expect to be long-term survivors – after starting with “7+3” induction therapy. Furthermore, and quite unthinkably even two decades ago, patients tolerate this combination well into their seventies.
- Ellison RR, Holland JF, Weil M. Arabinosyl cytosine: a useful agent in the treatment of acute leukemia in adults. Blood. 1968; 32(4):507-523. https://doi.org/10.1182/blood.V32.4.507.507PubMedGoogle Scholar
- Bernard J, Weil M, Boiron M, Jacquillat C, Flandrin G, Gemon MF. Acute promyelocytic leukemia: results of treatment by daunorubicin. Blood. 1973; 41(4):489-496. https://doi.org/10.1182/blood.V41.4.489.489PubMedGoogle Scholar
- Crowther D, Powles RL, Bateman CJ. Management of adult acute myelogenous leukaemia. Br Med J. 1973; 1(5846):131-137. https://doi.org/10.1136/bmj.1.5846.131PubMedPubMed CentralGoogle Scholar
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