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 Journal Article
| Authors: | Stone, R. M.; Mazzola, E.; Neuberg, D.; Allen, S. L.; Pigneux, A.; Stuart, R. K.; Wetzler, M.; Rizzieri, D.; Erba, H. P.; Damon, L.; Jang, J. H.; Tallman, M. S.; Warzocha, K.; Masszi, T.; Sekeres, M. A.; Egyed, M.; Horst, H. A.; Selleslag, D.; Solomon, S. R.; Venugopal, P.; Lundberg, A. S.; Powell, B. |
| Article Title: | 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 |
| 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. © 2015 by American Society of Clinical Oncology. |
| Keywords: | adult; controlled study; treatment outcome; aged; young adult; acute granulocytic leukemia; major clinical study; cancer combination chemotherapy; cytarabine; drug megadose; prospective study; randomized controlled trial; stem cell transplantation; continuous infusion; cancer mortality; cancer resistance; cancer regression; multicenter study; daunorubicin; open study; phase 3 clinical trial; induction chemotherapy; amonafide; very elderly; human; male; female; priority journal; article |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 33 |
| Issue: | 11 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2015-04-10 |
| Start Page: | 1252 |
| End Page: | 1257 |
| Language: | English |
| DOI: | 10.1200/jco.2014.57.0952 |
| PROVIDER: | scopus |
| PUBMED: | 25732165 |
| DOI/URL: | |
| Notes: | Export Date: 4 May 2015 -- Source: Scopus |
