73 P - Oral idarubicin (OIDA) in elderly patients (pts) with acute myelogenous Leukemia (AML): An opportunity?
1996
IDA, besides Its unique peculiarity of oral as well as I.v. administration, exhibits Intriguing potentials for (partially) reverting Pgp/mar -l –related MutiDrug Resistance (MDR), especially relevant in hematological malignancies, as well as for killing noncyling/testing bone narrow precursors, possibly via simulation of apoptosis. Compared to I.v. IDA, oiDA yields a twofold amount of its uniquely affective OH-13 metabolite, IDAOL, equally active and myelotoxic as the parent IDA. Thus, although oiDA cannot be meaningfully introduced in intensive chemotherapy (CT), it was proposed for elderly pts with AML conventionally, Pts over 60 are considered as elderly, and over all they had lower CR and higher toxic death rates compared to younger adults, even if recent report emphasize the need for Risk-adjusted treatment, tallored to the biological rather than chronological age of the individual pts. Based on data from published trials in elderly AML patients. Table Author/Year Patient Population Regimen(mg/m 2 ) CR CR/pts % CR median, duration, wks % Deafts on induction MST, wks Harousseau, 1989 >65 yrs, untreated oiDA 30×3d 8/20 40 21+ 25 20 Harousseau, 1991 >65 yrs, untreated oiDA 20×3d, LD Ara-C s.c. 13/32 41 15 19 23 Ruutu, 1994 >65 yrs, untreated ETI * vs TAD * 15/25 60 6/26 23 30 12 4 23 40 15 Pagano, 1991 65 yrs, untreated/pretreated oiDA 25×3d Ara-c s.c. 8/17 47 22 23 49(in responders) Helg, 1990 >65 yrs, untreated/pretreated oiDA 30×3d LD Ara-C s.c. 14/26 53 20 19 not available Total 58/120 48% CR TAD: 6-TG p.p. 200 mg/m 2 dialy × 5 d; Am- cC i.v. 200 mg/m 2 daily × 5 d; Denorubicin i.v, 60 mg/m 2 × 1d. * TI: VP-16 p.a. 180 mg/m 2 daily × 5 d; 6-TG p.a. 200 mg/m 2 daily × 5 d; oiDA 15 mg/m 2 daily × 5d. oiDA, both as a single-agent and as a component of fully or partially oral combinations with cytosine arobinoside (Ara-c), etopside (VP-16), or 6-thioguanine (6-TG), proved effective. However it should not be understood as attenuated CT, on account of significant myelotoxicity anyway preciuding outpatient treatment (especially at doses > 15 mg/m 2 dally × 3). Indeed, cumulated evidence appears to suggest use of hematopoietic support. Other, strictly investigational approaches are:1) Induction with chronic low-dose oiDA in poor risk pts, unit for aggressive/intensive CT, and 2)use of an oral regimen as postremission treatment following a standard “intensive” L.v, CT.
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