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1394 Part X: Malignant Myeloid Diseases Chapter 88: Acute Myelogenous Leukemia 1395

TABLE 88–6. Remission Induction for Acute Myelogenous Leukemia: Examples of Cytosine Arabinoside and Anthracycline
Antibiotic Combinations
Anthracycline Age Range in Complete Year of
Cytarabine Antibiotic ± Another Agent No. of Patients Years (Median) Remissions (%) Report Reference
100 mg/m , days 1–7 DNR 50 mg/m days 1–5 407 15–64 (47) 77.5 2011 596
2
2
100 mg/m , days 1–7 IDA 12 mg/m days 1–3 525 15–64 (47) 78.2 2011 596
2
2
100 mg/m , days 1–7 DNR 45 mg/m , days 1–3 330 17–60 (47) 57 2009 593
2
2
100 mg/m , days 1–7 DNR 90 mg/m , days 1–3 327 18–60 (48) 71 2009 593
2
2
200 mg/m , days 1–7 DNR 60 mg/m , days 1–3 200 16–60 (45) 72 2004 611
2
2
200 mg/m , days 1–7 DNR 60 mg/m , days 1–3 200 16–60 (45) 69 2004 611
2
2
Cladribine 5 mg/m , days 1–5
2
2
200 mg/m twice per DNR 50 mg/m , days 1, 3, 5 64 18–59 (46.5) 91 2003 609
2
day for 10 days (some Thioguanine 100 mg/m
2
in this report received twice per day, days 10–20
FLAG-IDA vs. H-DAT)
Gemtuzumab ozogamicin
2
3 mg/m , day 1
3 g/m every 12 h for 60 mg/m DNR daily for 122 Adults 80 2000 603
2
2
8 doses 2 days
100 mg/m daily for IDA 12 mg/m daily for 3 days 153 NR 63 2000 589
2
2
7 days (2 courses
always given)
500 mg/m by Mitoxantrone 12 mg/m for 133 15–70 (43) 60 1996 606
2
2
continuous infusion, 3 days
days 1–3, 8–10 Etoposide 200 mg/m days
2
8–10
2
100 mg/m daily for DNR 45 mg/m for 3 days 113 NR (55) 59 1992 588
2
7 days
100 mg/m daily for IDA 13 mg/m for 3 days 101 NR (56) 70 1992 588
2
2
7 days
DNR, daunorubicin; FLAG, fludarabine, cytarabine, and granulocyte colony-stimulating factor; H-DAT, hydroxydaunorubicin, cytarabine, and
thioguanine; IDA, idarubicin; NR, not reported.
All drugs are administered intravenously, except for thioguanine, which is administered orally. The reader is advised to consult the
original reports for details of induction, consolidation or continuation therapy, and ancillary therapy.
or an anthraquinone and cytarabine (see “Special Therapeutic Con- Choice of Anthracycline Development of drug resistance is
siderations: Acute Promyelocytic Leukemia” below for therapy of reduced with idarubicin relative to other anthracyclines. Idarubicin
APL). 588–617 Remission rates in the studies cited range from approxi- does not induce P-glycoprotein expression, but daunorubicin, doxoru-
mately 55 to 90 percent in adult subjects, depending on the composi- bicin, and epirubicin do. Idarubicin 12 mg/m gives better complete
2
590
tion of the population treated (Table 88–6). The two most important remission rates in younger adults than does daunorubicin 45 mg/m ,
2
variables are the age of the patients and the proportion of patients with each given for 3 days. Amsacrine, aclarubicin, and mitoxantrone give
therapy-induced leukemia or an antecedent clonal myeloid disease. In improved results over standard-dose daunorubicin. In older adults,
the studies listed in Table 88–6, the median age of the patient popu- mitoxantrone may reduce cardiotoxicity, but this is controversial. In
591
lations was much younger (approximately 50 years) than the median two randomized studies, high-dose daunorubicin (90 mg/m ) for 3 days
2
age of the population of AML patients at large (approximately 70 resulted in superior complete remission rates as compared to 45 mg/
years); thus the results cannot be generalized (see “Treatment of Older m for 3 days when combined with cytarabine. 592,593 When idarubicin
2
Patients” below). A combination of anthracycline and cytarabine has 12 mg/m was compared to daunorubicin 80 mg/m for 3 days in
2
2
been the standard induction therapy since 1973. 11,12 A now classic stan- patients 50 to 70 years of age, the remission rate with idarubicin was
dard induction regimen is cytarabine 100 mg/m daily by continuous 83 percent compared to 40 percent with daunorubicin. Another anal-
594
2
infusion on days 1 through 7 and daunorubicin at 45 to 90 mg/m on ysis of idarubicin compared with high-dose daunorubicin in patients
2
days 1 through 3, the “7 plus 3” regimen. Dose or schedule modula- with AML showed idarubicin to result in a higher remission rate but not
tion of the anthracycline or cytarabine, addition of other agents such as overall survival. In contrast, a randomized study showed no differ-
595
etoposide, in various schedules of administration, represent attempts to ence in remission and long-term efficacy between idarubicin 12 mg/m
2
improve upon results obtained with “7 plus 3” therapy. daily for 3 days as compared to daunorubicin, 50 mg/m daily for
2
Kaushansky_chapter 88_p1373-1436.indd 1395 9/21/15 11:01 AM