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Pharmaceutisch Weekblad. Scientific... Apr 1983Decomposition of vidarabine in a 5% glucose infusion fluid after steam sterilization was measured by HPLC and TLC analysis. After sterilization for 60 minutes at 100...
Decomposition of vidarabine in a 5% glucose infusion fluid after steam sterilization was measured by HPLC and TLC analysis. After sterilization for 60 minutes at 100 degrees C and 20 minutes at 120 degrees C no degradation could be observed. A slight but significant degradation was observed after sterilization for 60 minutes at 120 degrees C followed by storage for eight months. Assuming 5% loss of content to be acceptable, it was concluded that a vidarabine infusion fluid can be sterilized for 20 minutes at 120 degrees C and stored at room temperature for at least eight months afterwards.
Topics: Adenine; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Humans; Infusions, Parenteral; Vidarabine
PubMed: 6866715
DOI: 10.1007/BF01960076 -
Cancer Sep 2009Patients with purine analogue-refractory chronic lymphocytic leukemia (CLL) have short survival and limited treatment options. Defining the best salvage strategies for... (Review)
Review
Patients with purine analogue-refractory chronic lymphocytic leukemia (CLL) have short survival and limited treatment options. Defining the best salvage strategies for this population is challenging, because limited data are available from clinical trials, and because studies have enrolled mixed populations (patients with recurrent and refractory disease or patients with refractory disease and Richter transformation). Moreover, patients with refractory CLL have a high incidence of unfavorable molecular and clinical features, such as high-risk genomic profiles, unmutated immunoglobulin heavy-chain genes, expression of zeta-chain-associated protein kinase 70, and bulky lymphadenopathies. These patients are also severely immunosuppressed because of the underlying disease and the treatments received, and experience a high rate of infectious complications that pose an additional difficulty in selecting treatment. Despite these challenges, in parallel with better characterizations of the biologic features of refractory CLL, the number of available treatment modalities for this population has increased. Several chemoimmunotherapy combinations have been developed, and novel agents with a different mechanism of action are being investigated in clinical trials. Furthermore, allogeneic stem cell transplantation with nonmyeloablative conditioning regimens is a therapeutic strategy that is increasingly offered to patients with refractory CLL.
Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Resistance, Neoplasm; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Retreatment; Transplantation, Homologous; Vidarabine
PubMed: 19536902
DOI: 10.1002/cncr.24479 -
Drugs 2007Fludarabine (Fludara), a purine nucleoside analogue, has been extensively evaluated in the treatment of a number of lymphoproliferative malignancies, including various... (Review)
Review
Fludarabine (Fludara), a purine nucleoside analogue, has been extensively evaluated in the treatment of a number of lymphoproliferative malignancies, including various types of non-Hodgkin's lymphoma. Clinical studies have shown that fludarabine (alone, and particularly as a component of combination therapy) can result in high overall and complete response in adults with various types of non-Hodgkin's lymphoma, including follicular lymphoma. As mono- or combination therapy, intravenous fludarabine is as effective as several other standard treatment regimens in treatment-naive patients and is also effective in patients with recurrent or refractory disease. The efficacy of fludarabine therapy is improved with the use of rituximab, as part of the initial therapeutic regimen or as maintenance therapy, and deserves consideration. The once-daily oral formulation was effective in the treatment of patients with relapsed indolent B-cell non-Hodgkin's lymphoma; however, further studies are required to confirm its role and establish its efficacy relative to that of standard treatment in this patient population. Fludarabine has generally acceptable tolerability; however, it is associated with haematological adverse events, including myelosuppression. Fludarabine, therefore, provides a highly effective first- or second-line option in the treatment of non-Hodgkin's lymphoma.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Vidarabine
PubMed: 17661532
DOI: 10.2165/00003495-200767110-00008 -
Drugs Jun 1997Fludarabine is an antineoplastic agent which has been studied in patients with a variety of lymphoproliferative malignancies. Clinical evidence from comparative studies... (Comparative Study)
Comparative Study Review
Fludarabine is an antineoplastic agent which has been studied in patients with a variety of lymphoproliferative malignancies. Clinical evidence from comparative studies in chronic lymphocytic leukaemia (CLL) suggests that fludarabine is at least as effective as CAP (cyclophosphamide, doxorubicin and prednisone) or CHOP (cyclophosphamide, vincristine, doxorubicin and prednisone) in previously treated or chemotherapy-naive patients and significantly more effective than chlorambucil in terms of response rate and duration and survival in chemotherapy-naive patients. Promising results have also been reported with fludarabine-based combination therapy in the treatment of patients with CLL. In addition, sequential therapy with fludarabine and cytarabine has demonstrated good efficacy in the treatment of acute leukaemias, as has fludarabine monotherapy and combination therapy in low grade non-Hodgkin's lymphoma. A favourable cytoreductive response has been reported in patients with lymphoplasmacytoid lymphoma and in a smaller number of patients with cutaneous T cell lymphomas, CLL of T cell origin or prolymphocytic leukaemia. Recent data also support the use of fludarabine, either as a component of a nonmyeloablative conditioning regimen or in the attainment of minimal residual disease, in patients undergoing peripheral blood stem cell or bone marrow transplantation. The tolerability profile of fludarabine is similar to that of CAP, with the most common adverse events being granulocytopenia, thrombocytopenia, anaemia and infection. Alopecia and nausea/vomiting appear to be less frequent with fludarabine therapy than with CAP although the development of immune cytopenias is more frequent with fludarabine. Severe neurotoxicity has been reported with fludarabine but this is mostly confined to the use of high doses. Clinical experience therefore indicates that fludarabine is an effective and generally well-tolerated antineoplastic agent for the second-line treatment of advanced CLL. Recent data from comparative studies also support the earlier use of fludarabine in the treatment of chemotherapy-naive patients with CLL. Furthermore, results of available studies are increasingly highlighting an important future role for fludarabine in the treatment of acute leukaemias and low grade NHL and possibly other lymphoproliferative disorders, particularly when used as a component of combination chemotherapy.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Drug Synergism; Drug Tolerance; Hematologic Neoplasms; Humans; Vidarabine
PubMed: 9179529
DOI: 10.2165/00003495-199753060-00007 -
Nucleosides, Nucleotides & Nucleic Acids 2009In order to improve the oral bioavailability of Adenine 9-beta-D-arabinofuranoside (Vidarabine, also called ara A), an antiviral drug which is active against herpes...
In order to improve the oral bioavailability of Adenine 9-beta-D-arabinofuranoside (Vidarabine, also called ara A), an antiviral drug which is active against herpes simplex and varicella zoster viruses and the first agent to be licensed for the treatment of systematic herpes virus infection in man, the corresponding 5'-O-D-valyl ester derivative has been synthesized. Based on their physicochemical properties, 5'-O-valyl ara A has emerged as a potential prodrug candidate to improve the oral bioavailability of vidarabine. We describe in this paper a facile synthesis route for the prodrug and its physicochemical properties.
Topics: Absorption; Adenosine Deaminase; Animals; Antiviral Agents; Biological Availability; Cell Line, Tumor; Epithelial Cells; Humans; Intestinal Mucosa; Prodrugs; Rats; Vidarabine
PubMed: 19116869
DOI: 10.1080/15257770802581757 -
Leukemia & Lymphoma 1994Fludarabine is a prodrug that must enter cells and be phosphorylated to the nucleoside triphosphate, F-ara-ATP, to elicit biological activity. F-ara-ATP serves as an... (Review)
Review
Fludarabine is a prodrug that must enter cells and be phosphorylated to the nucleoside triphosphate, F-ara-ATP, to elicit biological activity. F-ara-ATP serves as an inhibitory alternative substrate in several key processes involved in DNA synthesis. The enzymes required in DNA synthesis and affected by F-ara-ATP are ribonucleotide reductase, DNA primase, DNA polymerases, 3'-5' exonuclease activity of DNA polymerases delta and epsilon, and DNA ligase I. The action of fludarabine on DNA replication provides a compelling rationale to use this agent for leukemias where target cells are actively synthesizing DNA, for example acute myelogenous leukemia. Additionally, the role of F-ara-ATP to potentiate the activity of deoxycytidine kinase makes it an appropriate candidate to use in combination with other nucleoside analogs which require deoxycytidine kinase for their activation. The present article reviews the effect of fludarabine on enzymes involved in DNA synthesis and the role of fludarabine in combination with arabinosylcytosine for the treatment of diseases other than indolent leukemias.
Topics: Acute Disease; Animals; Antineoplastic Agents; DNA Replication; Humans; Leukemia; Leukemia, Experimental; Mice; Vidarabine
PubMed: 7881348
DOI: 10.3109/10428199409052689 -
Leukemia Research Oct 2018
Topics: Anthracyclines; Drug Therapy, Combination; Humans; Leukemia, Myeloid, Acute; Vidarabine
PubMed: 30212655
DOI: 10.1016/j.leukres.2018.08.018 -
Journal of Clinical Oncology : Official... Oct 2003
Topics: Acute Disease; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Flow Cytometry; Humans; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Male; Middle Aged; Rituximab; Vidarabine
PubMed: 14512411
DOI: 10.1200/JCO.2003.99.090 -
Lancet (London, England) Oct 1993
Topics: Adult; Antineoplastic Agents; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Red-Cell Aplasia, Pure; Vidarabine
PubMed: 8105278
DOI: No ID Found -
Gastroenterologie Clinique Et Biologique 1987A randomized controlled study of one course of vidarabin was carried out in 30 patients with HBs Ag, HBe Ag, DNAp, positive chronic active hepatitis: 15 patients were... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
A randomized controlled study of one course of vidarabin was carried out in 30 patients with HBs Ag, HBe Ag, DNAp, positive chronic active hepatitis: 15 patients were treated with vidarabin given intravenously (15 mg/kg/day for 7 days then 7.5 mg/kg/day for 14 days); the other 15 patients received a placebo for 21 days. During treatment, DNA polymerase activity fell dramatically in 13 treated patients and in no controls (p less than 0.001). Six months after inclusion, ALT normalization was observed in 40 p. 100 of the treated patients and 6 p. 100 of the controls (p less than 0.05), a decrease in inflammatory activity on liver biopsies was observed in 70 p. 100 of the treated patients and 20 p. 100 of the controls (p less than 0.05), a permanent lost of DNA polymerase and of HBe Ag occurred in 33 p. 100 and 13 p. 100 of the treated patients and 20 p. 100 and 7 p. 100 of the controls, respectively. In addition, a second course of vidarabin was administered to the 12 patients who were still HBe Ag positive 6 months after the first course. During the next 6 months, 8 patients lost DNA polymerase and 4 lost HBe Ag. Altogether, the final score of durable inhibition of HBV replication was 11/15 (73 p. 100) within one year. The above results demonstrate that one course of vidarabin can significantly improve ALT and liver inflammatory activity but the effect upon HBV replication is only transient. A second course does however increase efficacy on HBV replication without additional side effects.
Topics: Adult; Clinical Trials as Topic; Female; Hepatitis B; Hepatitis B virus; Hepatitis, Chronic; Humans; Male; Middle Aged; Random Allocation; Vidarabine; Virus Replication
PubMed: 3308617
DOI: No ID Found