title: An extensive pharmacokinetic, metabolic and toxicological review of elderly patients under intensive chemotherapy for acute myeloid leukemia.
abstract: BACKGROUND
  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.
  
  
  METHODS
  This review discusses the pharmacokinetic (PK), metabolic and toxicological issues associated with antileukemic agents used to treat elderly patients (> 60 years) with AML.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Utah School of Medicine, Division of Clinical Pharmacology, Department of Pediatrics , 295 Chipeta Way, Salt Lake City , UT 84108 , USA +1 801 587 7404 ; +1 801 585 9410 ; Catherine.Sherwin@hsc.utah.edu.
authors.forename: Imit
authors.initials: I
authors.lastname: Kaur
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Constance
authors.forename: Ken M
authors.initials: KM
authors.lastname: Kosak
authors.forename: Michael G
authors.initials: MG
authors.lastname: Spigarelli
authors.forename: Catherine M T
authors.initials: CM
authors.lastname: Sherwin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000187:drug effects* / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000379:methods; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents
keywords: acute myeloid leukemia; chemotherapy; elderly; induction phase; metabolism; pharmacokinetics; toxicity