Pharmacokinetic Study of Single Doses of Oral Fludarabine Phosphate in Patients With “Low-Grade” Non-Hodgkin's Lymphoma and B-Cell Chronic Lymphocytic Leukemia

Foran, James M.; Oscier, David; Orchard, Jenny; Johnson, Stephen A.; Tighe, Mary; Cullen, Michael; Takats, P.G. de; Kraus, Christian; Klein, Marcus; Lister, T. Andrew

doi:10.1200/jco.1999.17.5.1574

Cited by 61 publications

(27 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…No comparison of oral versus IV administration has yet been published. Pharmacological studies show that 25 mg/kg fludarabine intravenously is equivalent to 40 mg/m 2 /d per os [23]. [24].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and long‐term toxicity of the rituximab‐fludarabine‐cyclophosphamide combination therapy in Waldenstrom's macroglobulinemia

et al. 2016

View full text Add to dashboard Cite

Waldenstrom's macroglobulinemia is generally treated with alkylating agents, purine analogs and monoclonal antibodies, alone or in combination. We report the outcomes of 82 patients (median age 61 years) treated with the RFC combination. Twenty-five patients were treatment-naive. RFC was administered every 4 weeks, for a median of five cycles. At treatment discontinuation, the overall response rate was 85.4%. The responses improved after treatment discontinuation in 25 patients, with a median time to best response achievement of 10.8 months, raising the major response rate (PR, VGPR and CR) from 64.6% to 76.8%. With a median follow-up of 47 months, the median progression-free survival time had not been reached (67% PFS at 48 months) and was influenced by age and treatment status before RFC. Likewise, the median time to next therapy had not been reached. Two cases of myelodysplastic syndrome/AML and 3 cases of transformation to aggressive lymphoma occurred. Thirteen patients died. The 3-year overall survival rate was 90%. Long-lasting cytopenias occurred in 19 patients. The RFC combination thus gave a high response rate and durable responses, even in heavily treatment-experienced patients. The high incidence of long-lasting cytopenia might be reduced by giving fewer courses and thereby minimizing myelotoxicity. Waldenstrom's macroglobulinemia (WM) is a rare B-cell malignancy characterized by the production of a monoclonal immunoglobulin (IgM) by welldifferentiated plasmacytic lymphocytes. Therapy is currently reserved for patients with constitutional symptoms, bone marrow or peripheral lymphoid organ involvement, and complications due to the monoclonal IgM component [1]. There is no consensus treatment strategy, and most clinical trials in WM have so far consisted of small phase II studies with widely differing inclusion and response criteria. Classically used chemotherapeutic agents consist of alkylating agents (chlorambucil, cyclophosphamide), purine analogues (fludarabine, 2-chlorodeoxyadenosine or 2CDA), a proteasome inhibitor (bortezomib) and bendamustine, used either alone or, more often, combined with immunotherapy (principally rituximab). A combination of cyclophosphamide and purine analogues offers synergistic activity, as DNA breaks caused by cyclophosphamide cannot be repaired in the presence of a purine analogue [2]. Studies of the cyclophosphamide and fludarabine combination in WM patients showed an overall response rate (ORR) of 55-77%, and a median time to treatment failure of around 24 months [3]. The fludarabine and rituximab combination has also been studied in a phase II trial, with an ORR of 95.3%, a 4-year progression-free survival rate (PFS) of 67%, and a median time to progression (TTP) of 77 months [4]. Rituximab, fludarabine, and cyclophosphamide combination therapy (RFC) yields a high response rate in patients with chronic lymphocytic leukemia (CLL), both as first-line treatment and after relapse [5,6], and is more effective than the FC combination in untreated CLL patients [7]. Until no...

show abstract

Section: Discussionmentioning

confidence: 99%

Efficacy and long‐term toxicity of the rituximab‐fludarabine‐cyclophosphamide combination therapy in Waldenstrom's macroglobulinemia

et al. 2016

View full text Add to dashboard Cite

show abstract

“…[28][29][30] In addition, oral formulation is more convenient, because it can be administered in an outpatient setting. 31,32 Therefore, in the current article, we present our experience with rituximab plus fludarabine as first-line treatment in patients with chemotherapy-naive, extranodal MALT lymphoma.…”

mentioning

confidence: 99%

Combination therapy with rituximab and intravenous or oral fludarabine in the first‐line, systemic treatment of patients with extranodal marginal zone B‐cell lymphoma of the mucosa‐associated lymphoid tissue type

Salar

Domingo‐Domenech

Estany

et al. 2009

Cancer

View full text Add to dashboard Cite

Poly(3‐hexylthiophene)‐b‐poly(4‐vinylpyridine) diblock copolymer was synthesized by RAFT polymerization of 4‐vinyl pyridine using a trithiocarbonate‐terminated poly(3‐hexylthiophene) macro‐RAFT agent. The optoelectronic properties and the morphology of the block copolymer blends with CdSe quantum dots were investigated. UV‐vis and fluorescence experiments were performed to prove the charge transfer between CdSe and poly(3‐hexylthiophene)‐b‐poly(4‐vinylpyridine) diblock copolymer. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011

show abstract

“…[1][2][3] Furthermore, fludarabine-containing combination regimens have also been used in the treatment of aggressive lymphomas as well as in acute leukemia. [4][5][6][7] Most recently, it has been incorporated into nonmyeloablative cytoreduction regimens and used as for immunosuppression in the novel mini-allogeneic transplant procedure used in recent years for a variety of hematological disorders.…”

mentioning

confidence: 99%

Fludarabine in combination with cyclophosphamide decreases incidence of GVHD and maintains effective graft-versus-leukemia effect after allogeneic stem cell transplantation in murine lymphocytic leukemia

Weiss¹,

Abdul-Hai²,

Or³

et al. 2003

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:Graft-versus-host disease (GVHD) is a severe disorder and despite therapeutic efforts to decrease its distressing clinical manifestations, treatment is still not optimal. Here we report the results of studies, in which the purine analogue, fludarabine phosphate, was used in an attempt to modify and decrease GVHD after stem cell transplantation, across major histocompatibility barriers for murine leukemia. B-cell leukemia (BCL-1) bearing (BALB/ c Â C57BL/6) F1 mice received two cycles of fludarabine (0.8 mg/kg) for 5 days every 2 weeks, followed by 400 mg/ kg cyclophosphamide i.p. Animals were then transplanted with C57BL/6 precursor cells and the development of leukemia and extent of GVHD was monitored both clinically and histopathologically. In the fludarabinetreated group, only nine of 28 (32%) mice developed leukemia, compared to 25 of 33 (76%) of control animals (P ¼ 0.0006 ). Mice treated with fludarabine-containing regimens prior to transplantation also had much less GVHD both clinically and at autopsy, while graft-versusleukemia appeared to be augmented in the same animals.

show abstract

Pharmacokinetic Study of Single Doses of Oral Fludarabine Phosphate in Patients With “Low-Grade” Non-Hodgkin's Lymphoma and B-Cell Chronic Lymphocytic Leukemia

Abstract: Oral doses of F-AMP can achieve an AUC(0-24h) of 2F-ara-A similar to intravenous administration, with dose-independent bioavailability. The tablet will greatly enhance the use of F-AMP in a palliative setting.

Cited by 61 publications

References 15 publications

Efficacy and long‐term toxicity of the rituximab‐fludarabine‐cyclophosphamide combination therapy in Waldenstrom's macroglobulinemia

Efficacy and long‐term toxicity of the rituximab‐fludarabine‐cyclophosphamide combination therapy in Waldenstrom's macroglobulinemia

Combination therapy with rituximab and intravenous or oral fludarabine in the first‐line, systemic treatment of patients with extranodal marginal zone B‐cell lymphoma of the mucosa‐associated lymphoid tissue type

Fludarabine in combination with cyclophosphamide decreases incidence of GVHD and maintains effective graft-versus-leukemia effect after allogeneic stem cell transplantation in murine lymphocytic leukemia

Contact Info

Product

Resources

About