Abstract
Purpose: Secondary acute myeloid leukemia (sAML), defined as AML arising after a prior myelodysplastic syndrome or after antineoplastic therapy, responds poorly to current therapies. It is often associated with adverse karyotypic abnormalities and overexpression of proteins that mediate drug resistance. We performed a phase III trial to determine whether induction therapy with cytarabine and amonafide L-malate, a DNA intercalator and non-ATP-dependent topoisomerase II inhibitor that evades drug resistance mechanisms, yielded a superior complete remission rate than standard therapy with cytarabine and daunorubicin in sAML. Patients and Methods Patients with previously untreated sAML were randomly assigned at a one-to-one ratio to cytarabine 200 mg/m2 continuous intravenous (IV) infusion once per day on days 1 to 7 plus either amonafide 600 mg/m2 IV over 4 hours on days 1 to 5 (A + C arm) or daunorubicin 45 mg/m2 IV over 30 minutes once per day on days 1 to 3 (D + C arm). Results The complete remission (CR) rate was 46% (99 of 216 patients) in A + C arm and 45% (97 of 217 patients) in D + C arm (P = .81). The 30- and 60-day mortality rates were 19% and 28% in A +C arm and 13% and 21% in D + C arm, respectively. Conclusion Induction treatment with A + C did not improve the CR rate compared with D + C in patients with sAML.
| Original language | English |
|---|---|
| Pages (from-to) | 1252-1257 |
| Number of pages | 6 |
| Journal | Journal of Clinical Oncology |
| Volume | 33 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - márc. 20 2015 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
- Medicine(all)
Cite this
Phase III open-label randomized study of cytarabine in combination with amonafide L-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. / Stone, Richard M.; Mazzola, Emanuele; Neuberg, Donna; Allen, Steven L.; Pigneux, Arnaud; Stuart, Robert K.; Wetzler, Meir; Rizzieri, David; Erba, Harry P.; Damon, Lloyd; Jang, Jun Ho; Tallman, Martin S.; Warzocha, Krzysztof; Masszi, T.; Sekeres, Mikkael A.; Egyed, Miklos; Horst, Heinz August; Selleslag, Dominik; Solomon, Scott R.; Venugopal, Parameswaran; Lundberg, Ante S.; Powell, Bayard.
In: Journal of Clinical Oncology, Vol. 33, No. 11, 20.03.2015, p. 1252-1257.Research output: Article
}
TY - JOUR
T1 - Phase III open-label randomized study of cytarabine in combination with amonafide L-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia
AU - Stone, Richard M.
AU - Mazzola, Emanuele
AU - Neuberg, Donna
AU - Allen, Steven L.
AU - Pigneux, Arnaud
AU - Stuart, Robert K.
AU - Wetzler, Meir
AU - Rizzieri, David
AU - Erba, Harry P.
AU - Damon, Lloyd
AU - Jang, Jun Ho
AU - Tallman, Martin S.
AU - Warzocha, Krzysztof
AU - Masszi, T.
AU - Sekeres, Mikkael A.
AU - Egyed, Miklos
AU - Horst, Heinz August
AU - Selleslag, Dominik
AU - Solomon, Scott R.
AU - Venugopal, Parameswaran
AU - Lundberg, Ante S.
AU - Powell, Bayard
PY - 2015/3/20
Y1 - 2015/3/20
N2 - Purpose: Secondary acute myeloid leukemia (sAML), defined as AML arising after a prior myelodysplastic syndrome or after antineoplastic therapy, responds poorly to current therapies. It is often associated with adverse karyotypic abnormalities and overexpression of proteins that mediate drug resistance. We performed a phase III trial to determine whether induction therapy with cytarabine and amonafide L-malate, a DNA intercalator and non-ATP-dependent topoisomerase II inhibitor that evades drug resistance mechanisms, yielded a superior complete remission rate than standard therapy with cytarabine and daunorubicin in sAML. Patients and Methods Patients with previously untreated sAML were randomly assigned at a one-to-one ratio to cytarabine 200 mg/m2 continuous intravenous (IV) infusion once per day on days 1 to 7 plus either amonafide 600 mg/m2 IV over 4 hours on days 1 to 5 (A + C arm) or daunorubicin 45 mg/m2 IV over 30 minutes once per day on days 1 to 3 (D + C arm). Results The complete remission (CR) rate was 46% (99 of 216 patients) in A + C arm and 45% (97 of 217 patients) in D + C arm (P = .81). The 30- and 60-day mortality rates were 19% and 28% in A +C arm and 13% and 21% in D + C arm, respectively. Conclusion Induction treatment with A + C did not improve the CR rate compared with D + C in patients with sAML.
AB - Purpose: Secondary acute myeloid leukemia (sAML), defined as AML arising after a prior myelodysplastic syndrome or after antineoplastic therapy, responds poorly to current therapies. It is often associated with adverse karyotypic abnormalities and overexpression of proteins that mediate drug resistance. We performed a phase III trial to determine whether induction therapy with cytarabine and amonafide L-malate, a DNA intercalator and non-ATP-dependent topoisomerase II inhibitor that evades drug resistance mechanisms, yielded a superior complete remission rate than standard therapy with cytarabine and daunorubicin in sAML. Patients and Methods Patients with previously untreated sAML were randomly assigned at a one-to-one ratio to cytarabine 200 mg/m2 continuous intravenous (IV) infusion once per day on days 1 to 7 plus either amonafide 600 mg/m2 IV over 4 hours on days 1 to 5 (A + C arm) or daunorubicin 45 mg/m2 IV over 30 minutes once per day on days 1 to 3 (D + C arm). Results The complete remission (CR) rate was 46% (99 of 216 patients) in A + C arm and 45% (97 of 217 patients) in D + C arm (P = .81). The 30- and 60-day mortality rates were 19% and 28% in A +C arm and 13% and 21% in D + C arm, respectively. Conclusion Induction treatment with A + C did not improve the CR rate compared with D + C in patients with sAML.
UR - http://www.scopus.com/inward/record.url?scp=84927136144&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84927136144&partnerID=8YFLogxK
U2 - 10.1200/JCO.2014.57.0952
DO - 10.1200/JCO.2014.57.0952
M3 - Article
C2 - 25732165
AN - SCOPUS:84927136144
VL - 33
SP - 1252
EP - 1257
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 11
ER -