Bortezomib Added to Daunorubicin and Cytarabine During Induction Therapy and to Intermediate-Dose Cytarabine for Consolidation in Patients With Previously Untreated Acute Myeloid Leukemia Age 60 to 75 Years: CALGB (Alliance) Study 10502
Autor: | Philip C. Amrein, William Blum, Peter M. Voorhees, Daniel J. DeAngelo, Martha Wadleigh, Eyal C. Attar, Richard Stone, Clara D. Bloomfield, Jonathan E. Kolitz, Bayard L. Powell, Guido Marcucci, Jeffrey L. Johnson, Richard A. Larson, Barry K. Moser, Gerard Lozanski, Eunice S. Wang |
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Rok vydání: | 2013 |
Předmět: |
Male
Oncology Cancer Research medicine.medical_specialty Myeloid Daunorubicin Pharmacology Disease-Free Survival Drug Administration Schedule Bortezomib immune system diseases hemic and lymphatic diseases Internal medicine Antineoplastic Combined Chemotherapy Protocols Peripheral Nervous System Original Reports medicine Humans neoplasms Aged business.industry Remission Induction Cytarabine Histocompatibility Antigens Class II Myeloid leukemia Induction chemotherapy Drug Synergism Consolidation Chemotherapy Induction Chemotherapy Middle Aged medicine.disease Boronic Acids Survival Analysis Antigens Differentiation B-Lymphocyte Leukemia Myeloid Acute Leukemia Treatment Outcome medicine.anatomical_structure Pyrazines Female business Follow-Up Studies medicine.drug |
Zdroj: | Journal of Clinical Oncology. 31:923-929 |
ISSN: | 1527-7755 0732-183X |
Popis: | Purpose The purpose of this study was to determine remission induction frequency when bortezomib was combined with daunorubicin and cytarabine in previously untreated older adults with acute myeloid leukemia (AML) and safety of bortezomib in combination with consolidation chemotherapy consisting of intermediate-dose cytarabine (Int-DAC). Patients and Methods Ninety-five adults (age 60 to 75 years; median, 67 years) with previously untreated AML (including therapy-related and previous myelodysplastic syndrome) received bortezomib 1.3 mg/m2 intravenously (IV) on days 1, 4, 8, and 11 with daunorubicin 60 mg/m2 on days 1 through 3 and cytarabine 100 mg/m2 by continuous IV infusion on days 1 through 7. Patients who achieved complete remission (CR) received up to two courses of consolidation chemotherapy with cytarabine 2 gm/m2 on days 1 through 5 with bortezomib. Three cohorts with escalating dose levels of bortezomib were tested (0.7, 1.0, and 1.3 mg/m2). Dose-limiting toxicities were assessed during the first cycle of consolidation. The relationship between cell surface expression of CD74 and clinical outcome was assessed. Results Frequency of CR was 65% (62 of 95), and 4% of patients (four of 95) achieved CR with incomplete platelet recovery (CRp). Eleven patients developed grade 3 sensory neuropathy. Bortezomib plus Int-DAC proved tolerable at the highest dose tested. Lower CD74 expression was associated with CR/CRp (P = .04) but not with disease-free or overall survival. Conclusion The addition of bortezomib to standard 3 + 7 daunorubicin and cytarabine induction chemotherapy for AML resulted in an encouraging remission rate. The maximum tested dose of bortezomib administered in combination with Int-DAC for remission consolidation was 1.3 mg/m2 and proved tolerable. Further testing of this regimen is planned. |
Databáze: | OpenAIRE |
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