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Oral fludarabine in untreated patients with B-cell chronic lymphocytic leukemia

Leukemia volume 24, pages 237–239 (2010)Cite this article

Fludarabine phosphate is among the most active drugs in the treatment of B-Cell Chronic Lymphocytic Leukemia (B-CLL), and as monotherapy, or in combination with cyclophosphamide and rituximab, has been widely adopted as frontline therapy for this disease. Pharmacokinetic studies show that oral fludarabine at a dose of 90 mg/m2/day produces an AUC(0−24 h) (AUC standing for area under the curve) comparable to that achieved with an intravenous dose of 50 mg/m2/day but with a lower Cmax1 with a reported efficacy comparable to the intravenous drug.2 In view of the convenience of administration and potential impact on resource utilization, the National Cancer Institute of Canada Clinical Trials Group initiated a phase II study of oral fludarabine in previously untreated patients with B-CLL who had an indication for therapy. The trial accrued 126 patients between 2002 and 2004. Confirmation of the diagnosis by flow cytometry was required. Analyses of known prognostic and predictive biomarkers including cytogenetic abnormalities, ZAP-70 expression and IgVH mutational status were performed. Cytogenetic abnormalities in peripheral blood mononuclear cells were identified by interphase FISH. The loci tested were ATM at 11q22.3, D135319 at 13q14.3, D12Z1 at 12p11.1-q11.1, and p53 at 17p13.1. A 13q34-specific sequence probe distinguished between monoallelic or biallelic loss and monosomy for chromosome 13.

All patients received oral fludarabine phosphate at a dose of 40 mg/m2/day for 5 days every 28 days for a planned six cycles, to a maximum of 8 cycles for patients not in CR after 6 cycles. Allopurinol was recommended for lymphocytosis ⩾100 × 109/l at the institution of therapy and hematopoietic growth factor support to permit scheduled dose delivery was not allowed. Dose reductions for hematologic toxicity graded according to the National Cancer Institute Working Group (NCI-WG) criteria were made starting in the second cycle.3

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Authors and Affiliations

  1. NCIC CTG, Kingston, Ontario, Canada

    C Shustik, A Sadura, L Shepherd & D Li

  2. Division of Hematology, McGill University Health Center, Montreal, Quebec, Canada

    C Shustik, A M V Duncan & D Rizi

  3. Cross Cancer Institute, Edmonton, Alberta, Canada

    A R Turner

  4. Hopital Charles LeMoyne, Greenfield Park, Quebec, Canada

    P Desjardins

  5. Queen Elizabeth II Health Sciences Centre (Victoria Site), Halifax, Nova Scotia, Canada

    L Fernandez

  6. The Moncton Hospital, Moncton, New Brunswick, Canada

    S Rubin

  7. University of Alberta Hospital, Edmonton, Alberta, Canada

    L Larratt

  8. Moores Cancer Center, UCSD, La Jolla, CA, USA

    L Rassenti & T Kipps

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  1. C Shustik
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Correspondence to C Shustik.

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Shustik, C., Turner, A., Desjardins, P. et al. Oral fludarabine in untreated patients with B-cell chronic lymphocytic leukemia. Leukemia 24, 237–239 (2010). https://doi.org/10.1038/leu.2009.205

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