Disease relevance of fludarabine phosphate

• Activity of fludarabine monophosphate in patients with advanced mycosis fungoides: a Southwest Oncology Group study [1].
• Differential induction of apoptosis by fludarabine monophosphate in leukemic B and normal T cells in chronic lymphocytic leukemia [2].
• Gastrointestinal toxicity was more common with the oral formulation than with IV fludarabine phosphate, but was generally mild to moderate and did not require treatment [3].
• Fludarabine phosphate has substantial activity against lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL) and low-grade non-Hodgkin's lymphoma (NHL) [4].
• CONCLUSION: Single-agent fludarabine phosphate is active in previously untreated LPC lymphoma and WM, with only moderate activity in MCL [5].

Psychiatry related information on fludarabine phosphate

• METHODS: Using fully major histocompatibility complex (MHC)-matched mouse models, we investigated whether donor T cells are essential for bone marrow engraftment under fludarabine phosphate and cyclophosphamide conditioning therapy [6].

High impact information on fludarabine phosphate

• Fludarabine monophosphate reduces the incidence and severity of graft-versus-host disease in a murine model of bone marrow transplantation [7].
• Efficacy and safety of oral fludarabine phosphate in previously untreated patients with chronic lymphocytic leukemia [3].
• PATIENTS AND METHODS: Patients with previously untreated B-cell chronic lymphocytic leukemia received 10-mg tablets of fludarabine phosphate to a dose of 40 mg/m(2)/d for 5 days, repeated every 4 weeks, for a total of six to eight cycles [3].
• Excellent in vivo bystander activity of fludarabine phosphate against human glioma xenografts that express the escherichia coli purine nucleoside phosphorylase gene [8].
• Pharmacokinetic study of single doses of oral fludarabine phosphate in patients with "low-grade" non-Hodgkin's lymphoma and B-cell chronic lymphocytic leukemia [9].

Chemical compound and disease context of fludarabine phosphate

• A phase I trial of combination fludarabine monophosphate and chlorambucil in chronic lymphocytic leukemia: a Southwest Oncology Group study [10].
• Fludarabine monophosphate (fludarabine) was initially discovered to have significant activity in indolent lymphoma and chronic lymphocytic leukemia (CLL) [11].
• Fludarabine phosphate is a purine antimetabolite approved for use in the management of patients with chronic lymphocytic leukemia [12].
• MATERIALS AND METHODS: Sixteen patients with hematologic malignancies underwent non-T-cell-depleted BMT following a low-intensity conditioning regimen consisting of fludarabine monophosphate 30 mg/m(2)/day for 6 days, busulfan 4 mg/kg/day for 2 days, anti-T lymphocyte globulin 10 mg/kg/day for 4 days [13].
• We have shown that patients transplanted with fludarabine phosphate, melphalan 100 mg/m2 and with CyA/MTX as post transplant immunosuppression can achieve good disease control with an acceptable level of toxicity [14].

Biological context of fludarabine phosphate

• The maximum tolerated dose for a 5-day infusion of fludarabine phosphate is thus 40 mg/m2/day [15].
• Because it shares many of the activities of Fludara in interfering with enzyme systems important in DNA and RNA synthesis and DNA repair, it is likely that this agent will also have a wider scope than is presently obvious [16].
• However, in the 2-fluoro-Ara AMP concentration range (0.26 micrograms/ml to 0.78 micrograms/ml) tested, five of eight (62.5%) tumors from untreated patients achieved IC50 compared to only seven of 18 (39%) tumors from treated patients [17].
• Fludara enhances kinetics of apoptosis and induces expression of a gene responsive to stress that regulates expression of a kinase involved in initiation of the apoptotic pathway [18].
• In this report, we examine changes in gene expression observed between freshly isolated CLL B cells and after maintenance in vitro with and without Fludara [18].

Anatomical context of fludarabine phosphate

• Phase I and II study of fludarabine phosphate in leukemia: therapeutic efficacy with delayed central nervous system toxicity [19].
• Phase II trial of fludarabine phosphate for adenocarcinoma of the pancreas. An Illinois Cancer Center study [20].
• The EBV-transformed cell line was resistant to classic DNA laddering induced with Fludara [18].
• A multicentre, open, non-comparative phase II study of a combination of fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor in relapsed and refractory acute myeloid leukaemia and de novo refractory anaemia with excess of blasts in transformation [21].
• Radiation rendered more cytotoxic by fludarabine monophosphate in a human oropharynx carcinoma cell-line than in fetal lung fibroblasts [22].

Associations of fludarabine phosphate with other chemical compounds

• 9-beta-D-Arabinofuranosyl-2-fluoroadenine 5'-monophosphate (NSC 312887) is a new purine antimetabolite that has been evaluated in a Phase I clinical trial [23].
• The studies described herein were aimed at defining the mechanism by which 9-beta-D-arabinofuranosyl-2-fluoroadenine 5'-triphosphate (FaraATP), the active intracellular metabolite of fludarabine phosphate, inhibits the synthesis of primer RNA and RNA-primed DNA by the polymerase alpha-primase complex [24].
• She was treated with a non-myeloablative preparative regimen that included fludarabine monophosphate (Flu, 120 mg/m(2)), cyclophosphamide (CY, 1200 mg/m(2)) and antithymocyte globulin (ATG, 15 mg/kg) followed by allogeneic peripheral blood stem cell transplantation (PBSCT) from her HLA-matched sister [25].
• Simultaneous sustained release of fludarabine monophosphate and Gd-DTPA from an interstitial liposome depot in rats: potential for indirect monitoring of drug release by magnetic resonance imaging [26].
• The adenine nucleoside analogue fludarabine phosphate in combination with cytosine-arabinoside (Ara-C) and granulocyte-colony stimulating factor (G-CSF) has recently proved effective in the treatment of poor-prognosis acute non-lymphoid leukaemia [27].

Gene context of fludarabine phosphate

• Other chemotherapeutic agents, such as fludarabine phosphate and topoisomerase II-active drugs, interact specifically with matrix-associated enzymes, such as DNA primase and the DNA topoisomerase II alpha isozyme [28].
• The greatest positive effect with Fludara was the upregulation of JNK1 [18].
• The overall median survival was 35.7 months with a significantly higher proportion of surviving cases among RAI 0-II stages, responders and patients receiving more than 5 FAMP cycles [29].
• Since beta-ara-A has been shown to be an effective inhibitor of potentially lethal damage (PLD) repair in cell culture system but ineffective in in vivo tumors, we carried out experiments to determine whether fludarabine phosphate which is not inactivated by adenosine deaminase potentiates the radiation effects on in vivo murine tumor [30].
• CD4 T-lymphocyte depletion, myelosuppression, and subsequent severe infections are the major side effects of fludarabine phosphate therapy [31].

Analytical, diagnostic and therapeutic context of fludarabine phosphate

• Phase II trial of fludarabine monophosphate as first-line treatment in patients with advanced follicular lymphoma: a multicenter study by the Groupe d'Etude des Lymphomes de l'Adulte [32].
• In addition, fludarabine monophosphate (Fludara) was sufficiently active in advanced refractory patients that approval for this agent in chronic lymphocytic leukemia was granted by the Food and Drug Administration without comparative clinical trials [16].
• INTERPRETATION AND CONCLUSIONS: The present report confirms the high efficacy of FAMP in previously pre-treated cases with acceptable toxicity and encourages its use as front-line treatment provided that the results of randomized trials demonstrate its superiority over conventional chemotherapy [29].
• Phase I clinical trials with fludarabine phosphate [33].
• Phase III clinical trials will be performed to compare Fludara I.V. with standard therapy versus the combination regimen in previously untreated patients with CLL [34].

References