Phase 1 study of epigenetic priming with decitabine prior to standard induction chemotherapy for patients with AML
| Autor: | Tania J. Curcio, Sebastian Mayer, Ewelina Morawa, Joseph M. Scandura, Cindy Ippoliti, Eric J. Feldman, Usama Gergis, Luis Villegas, Fabienne Brenet, Gail J. Roboz, J. Robi Bose, Michelle Moh, Ellen K. Ritchie |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Diarrhea Male Oncology medicine.medical_specialty Neutropenia Fever Daunorubicin Immunology Azacitidine Decitabine Kaplan-Meier Estimate Pharmacology Infections Biochemistry Drug Administration Schedule Young Adult Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Dose-Response Relationship Drug business.industry Cytarabine Induction chemotherapy Nausea Cell Biology Hematology DNA Methylation Middle Aged medicine.disease Leukemia Treatment Outcome Leukemia Myeloid Acute Disease Toxicity Female business medicine.drug |
| Zdroj: | Blood. 118:1472-1480 |
| ISSN: | 1528-0020 0006-4971 0053-8876 |
| Popis: | We conducted an open-label phase 1 study exploring the feasibility, safety, and biologic activity of epigenetic priming with decitabine before standard induction chemotherapy in patients with less-than-favorable risk of acute myelogenous leukemia (AML). We directly compared the clinical and DNA-hypomethylating activity of decitabine delivered at 20 mg/m2 by either a 1-hour infusion (Arm A) or a continuous infusion (Arm B) for 3, 5, or 7 days before a single, standard induction with infusional cytarabine (100 mg/m2 for 7 days) and daunorubicin (60 mg/m2 × 3 doses). Toxicity was similar to that of standard induction chemotherapy alone. Although we did not identify a maximum tolerated dose, there was more gastro-intestinal toxicity with 7 days of decitabine priming. Decitabine induced DNA hypomethylation at all dose levels and there was a trend toward greater hypomethylation in CD34+ bone marrow cells when decitabine was delivered by a short pulse (Arm A). Twenty-seven subjects (90%) responded to therapy: 17 with complete remission (57%) and 10 with partial remission (33%). Of the patients with partial remission to protocol treatment, 8 achieved remission to their next therapy, bringing the overall complete remission rate to 83%. We conclude that epigenetic priming of intensive chemotherapy can be safely delivered in an attempt to improve response rates. This trial was registered at www.clinicaltrials.gov as NCT00538876. |
| Databáze: | OpenAIRE |
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