TREATMENT WITH LOW-DOSE CYTARABINE IN ELDERLY PATIENTS (AGE 70 YEARS OR OLDER) WITH ACUTE MYELOID LEUKEMIA: A SINGLE INSTITUTION EXPERIENCE
Main Article Content
acute myeloid leukemia, low-dose cytarabine, treatment, elderly, prognosis.
Objectives: Low-dose cytarabine (LD-AraC) is still regarded as the standard of care in elderly patients with acute myeloid leukemia (AML) ‘unfit’ for intensive chemotherapy. In this study, we compared the efficacy of LD-AraC, in patients ? 70 years old, with that of intensive chemotherapy, best supportive care (BSC), or hypomethylating agents in a single institution experience.
Methods: Between 2000 and 2014, 60 patients received LD-AraC at 20 mg once or twice daily by subcutaneous injection for 10 consecutive days every 4-6 weeks. 85 patients were treated by intensive chemotherapy, 34 patients by hypomethylating agents, and 43 patients only by BSC.
Results: Complete remission rate with LD-AraC was 7% versus 56% with intensive chemotherapy and 21% with hypomethylating agents. Median overall survival (OS) of patients treated with LD-AraC was 9.6 months with 3-year OS of 12%. Survival with LD-AraC was better than with BSC only (P = 0.001). Although not statistically significant, intensive chemotherapy and hypomethylating agents tended to be better than LD-AraC in terms of OS (median: 12.4 months and 16.1 months, respectively). There was no clear evidence that a beneficial effect of LD-AraC was restricted to any particular subtype of patients, except for cytogenetics.
Conclusions: Despite a trend in favor of intensive chemotherapy and hypomethylating agents over LD-AraC, no real significant advantage could be demonstrated, while LD-AraC showed a significant advantage comparatively to BSC. This tends to confirm that LD-AraC can still represent a baseline against which new promising agents may be compared either alone or in combination.
2. Tilly H, Castaigne S, Bordessoule D, Sigaux F, Daniel MT, Monconduit M, et al. Low-dose cytosine arabinoside treatment for acute non-lymphocytic leukemia in elderly patients. Cancer 1985; 55:1633-6.
3. Roberts JD, Erschler WB, Tindle BH, Stewart JA. Low-dose cytosine arabinoside in the myelodysplastic syndromes and acute myelogenous leukemia. Cancer 1985; 56:1001-5.
4. Mufti GJ, Oscier DG, Hamblin TJ, Bell AJ. Low doses of cytarabine in the treatment of myelodysplastic syndrome and acute myeloid leukemia. N Engl J Med 1983; 309:1653-4.
5. Moloney WC, Rosenthal DS. Treatment of early acute non-lymphatic leukemia with low dose cytosine arabinoside. Haematol Blood Transfus 1981; 26:59-62.
6. Cheson BD, Jasperse DM, Simon R, Friedman MA. A critical apraisal of low dose cytosine arabinoside in patients with acute non-lymphocytic leukemia and myelodysplastic syndromes. J Clin Oncol 1986; 4:1857-64.
7. Degos L, Castaigne S, Tilly H, Sigaux F, Daniel MT. Treatment of leukemia with low-dose ara-C: a study of 160 cases. Semin Oncol 1985; 12:196-9.
8. Leyden M, Manoharan A, Boyd A, Cheng ZM, Sullivan J. Low dose cytosine arabinoside: partial remission of acute myeloid leukaemia without evidence of differentiation. Br J Haematol 1984; 57:301-7.
9. Housset M, Daniel MT, Degos L. Small doses of ara-C in the treatment of acute myeloid leukaemia: differentiation of myeloid leukaemia cells? Br J Haematol 1982; 51:125-9.
10. Burnett AK, Milligan D, Prentice AG, Goldstone AH, McMullin MF, Hills RK, et al. A comparison of low-dose cytarabine and hydroxuyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer 2007; 109:1114-24.
11. Löwenberg B, Zittoun R, Kerkhofs H, Jehn U, Abels J, Debusscher L, et al. On the value of intensive remission-induction chemotherapy in elderly patients of 65+ years with acute myeloid leukemia: A randomized phase III study of the European Organization for Research and Treatment of Cancer Leukemia Group. J Clin Oncol 1989; 7:1268-74.
12. Tilly H, Castaigne S, Bordessoulle D, Casassus P, Le Prisé PY, Tertian G, et al. Low dose cytarabine vs. intensive chemotherapy in the treatment of acute nonlymphocytic leukemia in the elderly. J Clin Oncol 1990; 8:272-9.
13. Kantarjian HM, Thomas XG, Dmoszynska A, Wierzbowska A, Mazur G, Mayer J, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol 2012; 30:2670-7.
14. Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, et al. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood 2013; 122:1384-94.
15. Burnett AK, Russell NH, Culligan D, Cavanagh J, Kell J, Wheatley K, et al. The addition of the farnesyl transferase inhibitor, tipifarnib, to low dose cytarabine does not improve outcome for older patients with AML. Br J Haematol 2012; 158:519-22.
16. Fenaux P, Mufti GJ, Hellström-Lindberg E, Santini V, Gattermann N, Germing U, et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol 2010; 28:562-9.
17. Dombret H, Seymour JF, Butrym A, Wierzbowska A, Sellestag D, Jang JH, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with > 30% blasts. Blood 2015; 126:291-9.
18. Klepin HD, Geiger AM, Tooze SB, Kritchevsky SB, Williamson JD, Pardee TS, et al. Geriatric assessment predicts survival for older adults receiving induction chemotherapy for acute myelogenous leukemia. Blood 2013; 121:4287-94.
19. Gupta V, Chun K, Yi QL, Minden M, Schuh A, Wells R, et al. Disease biology rather than age is the most important determinant of survival of patients ? 60 years with acute myeloid leukemia treated with uniform intensive therapy. Cancer 2005; 103:2082-90.
20. Fattoum J, Cannas G, Elhamri M, Tigaud I, Plesa A, Heiblig M, et al. Impact of age on treatment decision making in elderly patients with acute myeloid leukemia. Clin Lymphoma Myeloma Leuk 2015; [Epub ahead of print].
21. Alibhai SMH, Leach M, Gupta V, Tomlinson GA, Brandwein JM, Suarez Saiz F, et al. Quality of life beyond 6 months after diagnosis in older adults with acute myeloid leukemia. Crit Rev Oncol Hematol 2009; 69:168-74.
22. Rodriguez JN, Fernandez-Jurado A, Martino ML, Diéguez JC, Moreno MV, Quesada JA, et al. Acute myeloid leukemia in those over 70 years of age. Experience using low-dose ara-C treatment. Sangre 1998; 43:35-9.
23. Kantarjian H, Ravandi F, O’Brien S, Cortes J, Faderl S, Garcia-Manero G, et al. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood 2010; 116:4422-9.
24. Kadia TM, Faderl S, Ravandi F, Jabbour E, Garcia-Manero G, Borthakur G, et al. Final results of a phase 2 trial of clofarabine and low-dose cytarabine alterning with decitabine in older patients with newly diagnosed acute myeloid leukaemia. Cancer 2015; (Epub ahead of print).