Fludarabine for

A 73-year-old woman developed fever and cough 2 weeks after completing a third cycle of fludarabine for chronic lymphocytic leukemia. A chest X-ray showed multiple pulmonary nodules and a biopsy showed a mononuclear interstitial infiltrate without evidence of malignant, infectious, granulomatous, or vascular causes. Her symptoms and pulmonary nodules resolved after treatment with glucocorticoids (4). 

Trojan A, Meier R, Licht A, Tavema C. Eosinophilic pneumonia after administration of fludarabine for the treatment of non-Hodgkin s lymphoma. Arm Hematol 2002 81(9) 535-7. 

A 62-year-old woman with no history of liver disease developed an episode of self-limited acute hepatitis following consumption of 2 liters of noni juice over a 3-month period. A percutaneous liver biopsy revealed acute hepatitis consistent with an idiosyncratic drug reaction. Elevated levels of AST, ALT, and bilirubin were observed and returned to normal after cessation of noni. The woman had been treated the previous year with fludarabine for chronic B-cell leukemia (Stadlbauer et al. 2005). 

Classen CF, Sigi-Kraetzig M, Hoffmann GF, Simmonds HA, Fairbanks LD, Debatin KM, Friedrich W. Successful HLA-identical bone marrow transplant in a patient with PNP deficiency using bisulfan and fludarabine for conditioning. Bone Marrow Transplantation 2001 28 93-96... 

Fludarabine-based chemotherapy is used increasingly as first-line therapy for younger patients with chronic lymphocytic leukemia (CLL). 

The most commonly used dose for fludarabine is 20 mg/m2 intravenously daily for 5 consecutive days, whereas chlorambucil can be taken daily as an oral tablet with the dose ranging from 4 to 10 mg/day.21 Fludarabine is associated with more toxicities than chlorambucil, including myelosuppression and prolonged immunosuppression.19 Resulting infectious complications may occur during the periods of prolonged immunosuppression. The ease of administration and limited side effects make chlorambucil a practical option for symptomatic elderly patients who require palliative therapy... 

Fludarabine (Fludara) Myelosuppression prolonged immunosuppression resulting in secondary infectious complications edema neurotoxicity Dose 20 mg/m2 IV daily for S days. 

AS is a 65-year-old woman with relapsed acute myelogenous leukemia. PMH is significant for type II diabetes and renal insufficiency (CrCI 20 mL/minute). She is day +1 from a nonmyeloablative HCT with fludarabine (30 mg/m2 per day IV for 3 days) and total-body irradiation preparative regimen and a graft from a full HLA-matched sibling. 

Repeat every 28 days for 2 cycles Fludarabine Fludarabine 25 mg/M2 IV days 1-5... 

Several cell lines were screened for their response to three standard chemotherapy drugs fludarabine, vincristine, and Gleevec decreases in the mean optophoretic distance of Bcr-Abl positive cell line K-562 with no effect in the other cell lines demonstrate that the downshift in mean displacement is specific to the presence of the Bcr-Abl oncoprotein fludarabine, however, was ineffective in causing a decrease in the optophoretic displacement of the K-562 cell line, but showed an effect in the other four cell lines mobility values for each cell in the population have been taken and averaged, but data on subsets of the cells can still be extracted and further analyzed. 

The optophoretic response of the cells from two chronic lymphocytic leukemia (CLL) patients, showing fludarabine EC50 values below 0.1 (ig/m L, which is over a log lower than the EC50 values obtained for the four control individuals shown in Figure 7.9, demonstrating the increased sensitivity of the CLL tumor cells to fludarabine relative to normal cells exposed to the drug. 

Campath was given accelerated approval on the basis of response rate. The pivotal trial was a study in 93 pahents who had been previously treated with an alkylating agent and whose disease had progressed on treatment with fludarabine. The FDA requested a follow-up sfudy for full approval of Campafh by randomizing patients between Campath and chlorambucil (Leukeran) as front-line therapy This trial is ongoing. Thus, Campath has had a convenhonal development approach. 

Some lymphomas, for example, are related to overexpression of Bcl-2. Antisense oligonucleotides are specially designed to target the overexpression of Bcl-2. Oblimersen (Genasense) is an antisense drug by Genta to block Bcl-2 production and enhance the efficacy of other standard chemotherapy drugs such as paclitaxel, fludarabine, irinotecan, and cyclophosphamide. 

For the purpose of this study, PHA-767491 (a Cdc7/CDK9 inhibitor, final concentration 5 pM), fludarabine (nucleoside analogue, final concentration 10 pM), and bortezomib (pro-teasome inhibitor, final concentration 30 nM) were chosen as... 

Fludarabine (Fludara ) is a 2-fluorocytarabine (Fig. 34) which inhibits the DNA biosynthesis via the inhibition of DNA polymerase a and of RDPR. It is clinically used for the treatment of leukaemia (chronic lymphomytic leukaemia, CLL). 

The fluorine atom can be present in position 5 in uracil derivatives, or in position 1 in that of purine, as in fludarabine, which is used in the treatment of some leukemias (Figure 6.14 cf. Chapter 8). Nucleoside derivatives of fluorouracil (e.g., capecitabine) are prodrugs that allow the oral administration of 5-FU in cancer chemotherapy. The mechanism of action of these nucleosides is detailed in Chapters 7 and 8. Nucleosides having a trifluoromethylated base have been described for example, trifluridine is active on herpesvirus (Figure 6.14). 

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