Researchers from Poland have reported that the addition of cladribine to standard daunomycin/cytoarabine improves the complete remission (CR) rate and survival of newly diagnosed younger patients (60 years of age or younger) with acute myeloid leukemia (AML). The details of this Phase III randomized trial were reported at the 50th annual meeting of the American Society of Hematology on December 8, 2008 in San Francisco.[1]
Cladribine (2-CDA) is a purine analog with immunosuppressive properties that is the preferred first-line treatment of hairy cell leukemia. It chemically mimics nucleoside adenosine and inhibits adenosine deaminase, which interferes with DNA synthesis. Recently, new formulation of this agent has been developed for subcutaneous and oral administration. 2-CdA is widely established as first-line standard treatment for hairy cell leukemia. Several clinical trials have demonstrated that cladribine used alone or in combination with other cytotoxic drugs has efficacy and acceptable toxicity profile in the treatment of chronic lymphocytic leukemia, Waldenström macroglobulinemia, low-grade non-Hodgkin's lymphoma, and AML. Previous studies from Poland have shown that a regimen of cladribine, cytarabine, and mitoxantrone produces a complete response rate of 58% in patients with relapsed AML.[2]
Researchers affiliated with the Polish Adult Leukemia Group reported the outcomes of a randomized Phase III trial comparing induction therapy of AML in 673 newly diagnosed patients. The groups studied included:
- Standard daunomycin/cytarabine (DA)
- DA plus fludarabine (DAF)
- DA plus cladribine (DAC)
All patients received consolidation therapy. The following table summarizes the main findings of this study:
Table 1: Comparison of induction therapies for AML
| DA | DAF | DAC |
CR after one cycle | 51% | 55% | 63% |
Final CR rate | 57% | 60% | 68% |
Overall survival | 39% | 36% | 51% |
Leukemia-free survival | 32% | 41% | 51% |
| | | |
Early deaths were similar between the three groups (8-10%). These authors concluded that cladribine improved the CR rate and overall survival of newly diagnosed younger adults with AML.
Comments: These data suggest that cladribine can be added to standard DA induction without increasing toxicity. This is important because there has been little recent progress in induction therapy for AML.
References:
[1] Grosicki S, Kyrc-Krzemien S, Kuliczowski K, et al. Addition of cladribine to the standard daunorubicine-cytarabine (DA 3+7) remission induction protocol (DAC) contrary to adjunct of fludarabine (DAF) improves the overall survival in untreated adults with acute myeloid leukemia up to yo Y: A multicenter, randomized, phase III PALG AML 1/2004 DAF/DAC/DA Study in 673 patients. Blood. 2008;112:55, abstract number 133.
[2] Wierzowska A, Robakt T, Pluta A, et al. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. European Journal of Haematology. 2008;80:1115-1126.
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