Clinical Trials

Remission induction therapy for older adults with AML is no panacea, with 5-year survival rates resembling those of patients with advanced lung cancer.2 It is thus reasonable to consider investigational agents for older AML patients up front, particularly as these patients have a disease that resembles the advanced MDS or secondary AML.22 88 Potential targets for antileukemia therapy are explained in more detail in

Chapter 9. They include specific signaling molecules required for the maintenance of the leukemic state, such as tyrosine kinases; over expression of bcl-2, an antiapoptosis signal; DNA methylation, associated with suppression of regulatory genes and with disease progression; indirect pathways that maintain leuke-mogenesis, including angiogenesis and drug resistance; and investigational agents with mechanisms of action that differ from anthracyclines, anthracene-diones, and ara-C, such as nucleoside analogs, farnesyl transferase inhibitors, and MDR modulators.89-95

LOW-DOSE CHEMOTHERAPY/SUPPORTIVE CARE

In the setting of a poor functional age, serious comor-bid medical conditions, and particularly patient preference, less intensive chemotherapy or aggressive supportive care may be more appropriate treatment options. Drugs such as hydroxyurea (generally given in doses of 500-3000 mg/day, adjusted to the degree of leukocytosis and/or treatment-related thrombocytopenia) and low-dose ara-C (at a dose of 10 mg/m2) are well tolerated and will reduce leukocytosis for a period of time, though neither will impact survival.96 We use the phrase aggressive supportive care to emphasize that symptoms will be treated vigorously and to distinguish this modality from hospice. Blood and platelet transfusions should be administered to alleviate symptoms stemming from anemia and thrombocytopenia, and antibiotics initiated when appropriate. In addition, integrative therapies such as Reike, therapeutic touch, and herbal medicines may be used by the willing patient. These latter interventions often can be facilitated with involvement of a multidisciplinary team of physicians, nurses, case managers, social workers, therapists, and clergy. Hospice services should be instituted within 6 months of anticipated demise, though some hospice organizations prohibit blood product transfusions, which we consider to be palliative in this population and which may result in improved quality of life in terminal cancer patient populations.97

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