An extensive pharmacokinetic, metabolic and toxicological review of elderly patients under intensive chemotherapy for acute myeloid leukemia
- 13 October 2014
- journal article
- review article
- Published by Informa Healthcare in Expert Opinion on Drug Metabolism & Toxicology
- Vol. 11 (1), 53-65
- https://doi.org/10.1517/17425255.2015.972934
Abstract
Acute myeloid leukemia (AML) is a clonal hematological malignancy characterized by accumulation of poorly differentiated and immature blast cells in bone marrow and blood circulation. The initiation of intensive chemotherapy is necessary to control further progression of the disease. Therapeutic success is less common in older patients (> 65 years) than it is in younger patients with AML. Cytarabine in combination with an anthracycline has been the mainstays of AML therapy for many years and continues to serve as the foundation for the current standard therapeutic regimen. This review discusses the pharmacokinetic (PK), metabolic and toxicological issues associated with antileukemic agents used to treat elderly patients (> 60 years) with AML. Profound and predictable changes often occur with age and can have effects on drug metabolism, PK and toxicity with consequences bearing on overall efficacy. Few studies focus specifically on elderly patients with AML, but modifications to intensive induction therapy may be beneficial as the current number and rate of individuals achieving complete remission of the disease remains low. Therapeutic options, for the treatment of AML, have remained static for many years, but it has become clear that among elderly patients with AML, improved antileukemic therapy is greatly needed.Keywords
This publication has 100 references indexed in Scilit:
- The Origin and Evolution of Mutations in Acute Myeloid LeukemiaCell, 2012
- Drug resistance: Still a daunting challenge to the successful treatment of AMLDrug Resistance Updates, 2012
- Prognostic Relevance of Integrated Genetic Profiling in Acute Myeloid LeukemiaThe New England Journal of Medicine, 2012
- Clonal Architecture of Secondary Acute Myeloid LeukemiaThe New England Journal of Medicine, 2012
- A phase 2 study of lenalidomide monotherapy in patients with deletion 5q acute myeloid leukemia: Southwest Oncology Group Study S0605Blood, 2011
- Challenges in Treating Older Patients with Acute Myeloid LeukemiaJournal of Oncology, 2010
- Aberrant CpG island methylation in acute myeloid leukemia is accentuated at relapseBlood, 2008
- The leukemic stem cellBest Practice & Research Clinical Haematology, 2007
- CD33 expression and P-glycoprotein–mediated drug efflux inversely correlate and predict clinical outcome in patients with acute myeloid leukemia treated with gemtuzumab ozogamicin monotherapyBlood, 2007
- Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cellNature Medicine, 1997