Arsenic and Old Lace: Novel Approaches in Elderly Patients With Acute Myeloid Leukemia

https://doi.org/10.1053/j.seminhematol.2008.07.005Get rights and content

Arsenic has been used for more than 2,000 years in the treatment of a variety of medical conditions, including plague, hysteria, syphilis, and cancer. Numerous potential mechanisms of action have been identified. Arsenic trioxide has remarkable efficacy in acute promyelocytic leukemia and is approved by the US Food and Drug Administration for this indication. It has also been studied in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma and has limited single-agent efficacy in these diseases. We have completed a phase I/II trial of arsenic trioxide combined with low-dose ara-C (LDAC) in 49 patients with Int-2/high-risk MDS and 64 patients age 60 years and older with untreated AML. The regimen was generally well tolerated and complete remissions were observed in both MDS and AML patients, including in patients with poor baseline performance status and unfavorable cytogenetics. Manuscript has been accepted for publication.

Section snippets

Elderly AML Patients

AML carries a dismal prognosis in elderly patients, and conventional chemotherapy strategies are often both ineffective and toxic. The well-known combination of 7 days of infusional cytarabine and 3 days of daunorubicin has been the standard of care for many years, but is not a feasible option for many older patients with AML. Low-dose ara-C (LDAC) has been included in the literature since the 1960s and is a frequently used lower intensity alternative to conventional induction. LDAC is

Conclusions

Arsenic trioxide is a highly effective agent in APL. Its multifaceted mechanism of action and favorable toxicity profile make it an attractive choice for other hematologic malignancies, but single-agent efficacy has been limited. Treatment with arsenic trioxide and LDAC has had promising preliminary results in older patients with AML and further efforts to optimize this regimen are underway in AML, myelofibrosis, and advanced myeloproflierative diseases.

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    Citation Excerpt :

    There is a paucity of clinical trials in elderly patients and a general lack of data regarding outcomes of cytotoxic therapy for older patients with higher-risk MDS [9]. Even the definition of “elderly” varies widely, with patients over age 60, 65, or 70 years of age considered “elderly” in published studies [10–12]. In the absence of clear guiding data, clinical decisions may be extrapolated from data in older patients with AML [12], as it has been suggested that in older patients, higher-risk MDS and AML are two points on the biological continuum of the same disease [2].

STATEMENT OF CONFLICT OF INTEREST: Research support/Principal Investigator: Cephalon; Consultant/Scientific Advisory Board: Cephalon.

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