TY - JOUR
T1 - Comparison of idarubicin + ara-C-, fludarabine + ara-C-, and topotecan + ara-C-based regimens in treatment of newly diagnosed acute myeloid leukemia, refractory anemia with excess blasts in transformation, or refractory anemia with excess blasts
AU - Estey, Elihu H.
AU - Thall, Peter F.
AU - Cortes, Jorge E
AU - Giles, Francis J.
AU - O'Brien, Susan
AU - Pierce, Sherry A.
AU - Wang, Xuemei
AU - Kantarjian, Hagop M.
AU - Beran, Miloslav
PY - 2001/12/15
Y1 - 2001/12/15
N2 - It has been unclear whether regimens containing topotecan + ara-C (TA) or fludarabine + ara-C (FA) ± idarubicin are superior to regimens containing idarubicin + ara-C(IA) without either fludarabine or topotecan for treatment of newly diagnosed acute myeloid leukemia (AML), refractory anemia with excess blasts in transformation (RAEB-t), or RAEB. Of 1279 patients treated here for these diagnoses between 1991 and 1999, 322 received IA regimens, 600 FA regimens, and 357 TA regimens. All regimens used ara-C doses of 1 to 2 gm/m2/d, given by continuous infusion in IA, and over 2 to 4 hours in FA and TA. Complete remission (CR) rates were lower with FA (55%) and TA (59%) than with IA (77%). Both event-free survival (EFS) in CR and survival were shorter: median EFS in CR (95% confidence interval) was 63 weeks (range, 55-76 weeks) for IA, 40 (range, 31-46 weeks) for FA, and 36 (range, 27-44 weeks) for TA; median survival was 77 weeks (range, 57-88 weeks) for IA, 30 (range, 27-35 weeks) for FA, and 41 (range, 35-50 weeks) for TA. These trials were not randomized, and patients with worse prognoses were disproportionately given the FA and TA regimens. Nonetheless, after accounting for prognosis the FA and TA regimens remained highly significantly associated with lower CR rates, shorter EFS in CR, and shorter survival. Accounting for possible effects of individual trials within each of the IA, FA, and TA groups did not alter these findings. It is unlikely that, as given here, either FA or TA is, in general, superior to IA, highlighting the need for new treatments.
AB - It has been unclear whether regimens containing topotecan + ara-C (TA) or fludarabine + ara-C (FA) ± idarubicin are superior to regimens containing idarubicin + ara-C(IA) without either fludarabine or topotecan for treatment of newly diagnosed acute myeloid leukemia (AML), refractory anemia with excess blasts in transformation (RAEB-t), or RAEB. Of 1279 patients treated here for these diagnoses between 1991 and 1999, 322 received IA regimens, 600 FA regimens, and 357 TA regimens. All regimens used ara-C doses of 1 to 2 gm/m2/d, given by continuous infusion in IA, and over 2 to 4 hours in FA and TA. Complete remission (CR) rates were lower with FA (55%) and TA (59%) than with IA (77%). Both event-free survival (EFS) in CR and survival were shorter: median EFS in CR (95% confidence interval) was 63 weeks (range, 55-76 weeks) for IA, 40 (range, 31-46 weeks) for FA, and 36 (range, 27-44 weeks) for TA; median survival was 77 weeks (range, 57-88 weeks) for IA, 30 (range, 27-35 weeks) for FA, and 41 (range, 35-50 weeks) for TA. These trials were not randomized, and patients with worse prognoses were disproportionately given the FA and TA regimens. Nonetheless, after accounting for prognosis the FA and TA regimens remained highly significantly associated with lower CR rates, shorter EFS in CR, and shorter survival. Accounting for possible effects of individual trials within each of the IA, FA, and TA groups did not alter these findings. It is unlikely that, as given here, either FA or TA is, in general, superior to IA, highlighting the need for new treatments.
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U2 - 10.1182/blood.V98.13.3575
DO - 10.1182/blood.V98.13.3575
M3 - Article
C2 - 11739159
AN - SCOPUS:0035895052
SN - 0006-4971
VL - 98
SP - 3575
EP - 3583
JO - Blood
JF - Blood
IS - 13
ER -