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Leukemia & Lymphoma 1993The success of fludarabine as a single agent for therapy of chronic lymphocytic leukemia suggested its use in other leukemias such as adult acute myelogenous leukemia.... (Review)
Review
The success of fludarabine as a single agent for therapy of chronic lymphocytic leukemia suggested its use in other leukemias such as adult acute myelogenous leukemia. Because doses that are tolerated in the clinic were not effective in the treatment of acute myelogenous leukemia, our approach was to combine low dose fludarabine with other active agents such as arabinosylcytosine (ara-C). This is also based on the rationale that fludarabine pretreatment modulates the metabolism of ara-C resulting in potentiation of the accumulation of its triphosphate. Improved response rates and clinical efficacy of this combination further suggested combining this couplet with DNA damaging agents, because the active triphosphates of both these analogs inhibit replication and repair processes of DNA synthesis.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Acute; Vidarabine
PubMed: 8124234
DOI: 10.3109/10428199309064255 -
Blood Reviews May 2007Fludarabine-based regimens have become an increasingly popular first-line approach for symptomatic patients with chronic lymphocytic leukemia. Compared with... (Review)
Review
Fludarabine-based regimens have become an increasingly popular first-line approach for symptomatic patients with chronic lymphocytic leukemia. Compared with chlorambucil, fludarabine alone or in combination with cyclophosphamide or rituximab yields higher response rates, higher complete remission rates, and more durable progression-free survival. Immunotherapy and chemoimmunotherapy also have the potential to increase the depth of remission as assessed by flow cytometry or molecular techniques. An overall survival advantage with any one particular regimen has not yet been demonstrated. Progress with fludarabine-based regimens, monoclonal antibodies, chemoimmunotherapy, and high-dose therapy for previously untreated patients is reviewed. Fluorescent in situ hybridization and immunoglobulin variable heavy-chain sequencing now permit more individualized risk assessment. Examples of possible treatment algorithms based on risk category are explored. How to tailor treatment based on these newer prognostic factors remains a central, as yet unanswered management question.
Topics: Antineoplastic Combined Chemotherapy Protocols; Disease Management; Humans; Immunotherapy; Leukemia, Lymphocytic, Chronic, B-Cell; Risk Assessment; Treatment Outcome; Vidarabine
PubMed: 17097783
DOI: 10.1016/j.blre.2006.10.001 -
Polski Tygodnik Lekarski (Warsaw,...
Review
Topics: Animals; Antineoplastic Agents; Humans; Leukemia; Lymphoma; Neoplasms, Experimental; Vidarabine; Waldenstrom Macroglobulinemia
PubMed: 1845714
DOI: No ID Found -
The Journal of Antimicrobial... Jun 1988One hundred and thirty-four patients with recurrences of genital herpes were randomized in a double-blind trial to receive self-applied topical therapy with either... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
One hundred and thirty-four patients with recurrences of genital herpes were randomized in a double-blind trial to receive self-applied topical therapy with either vidarabine sodium phosphate in an aqueous gel or placebo gel. No significant differences were noted between the two groups in the duration of viral shedding, in the time to healing of the treated recurrence, in the interval between recurrences, or in the number of recurrences.
Topics: Administration, Topical; Adolescent; Adult; Clinical Trials as Topic; Double-Blind Method; Female; Herpes Genitalis; Humans; Male; Middle Aged; Random Allocation; Recurrence; Vidarabine
PubMed: 3045069
DOI: 10.1093/jac/21.6.801 -
Pediatric Annals Jun 1986The above discussion is not intended to be exhaustive but rather to discuss several compounds which are particularly promising at this time. There is no question that... (Review)
Review
The above discussion is not intended to be exhaustive but rather to discuss several compounds which are particularly promising at this time. There is no question that great strides have been made in the development of antiviral compounds over the past couple of decades. Many questions remain unanswered such as long-term effects on the host, possible emergence of resistant viruses, optimal routes of administration, and the proper regimens for particular viruses and diseases. In addition, current studies are evaluating combinations of antiviral agents as well as combination therapy involving interferon or antibody or immunity stimulants along with an antiviral agent. Surprising progress has been made to date resulting not only in new therapeutic modalities but promising a new era of progress.
Topics: Acyclovir; Amantadine; Antiviral Agents; DNA Viruses; Humans; Infant; Infant, Newborn; RNA Viruses; Ribavirin; Vidarabine; Virus Diseases
PubMed: 3523402
DOI: 10.3928/0090-4481-19860601-06 -
Annals of the New York Academy of... Mar 1977Abrabinosyl-N6-hydroxyadenine (ara-HA) was tested for its antiherpesvirus and immunosuppressive activities in vivo and in vitro. Mouse strains were used that had been...
Abrabinosyl-N6-hydroxyadenine (ara-HA) was tested for its antiherpesvirus and immunosuppressive activities in vivo and in vitro. Mouse strains were used that had been shown earlier to be very susceptible to intraperitoneal (i.p.) or intracerebral (i.c.) inoculation of a virulent strain of herpes simplex virus Type 1 (HSV-1). Susceptible mice were inoculated i.p. or i.c. with a stock pool of HSV-1 and treated with ara-HA (i.p.) beginning at least 24 hr later. The mice were given a 10-day course of drugs and followed for at least 21 days. Similar experiments were carried out with ara-A for comparative purposes. Ara-HA was found to protect mice inoculated with HSV-1 significantly better than ara-A. Lower concentrations of drugs were required and a higher percentage survived. Later challenge of the ara-HA-treated mice with HSV-1 demonstrated that these mice had become immune to HSV-1, indicating that the immune system is not severely affected by this course of ara-HA. A 10-day course of ara-HA, which was found to protect mice from 100 LD50 of HSV-1, reduced the capacity of the mouse lymphocytes to respond to allogeneic cells only slightly. In vitro ara-HA inhibited HSV-1 replication as well as proliferation of lymphocytes exposed to mitogen.
Topics: Animals; Antiviral Agents; Herpes Simplex; Immunity; Immunologic Techniques; Male; Mice; Mice, Inbred A; Mice, Inbred BALB C; Mice, Inbred C57BL; Simplexvirus; Vidarabine; Virus Replication
PubMed: 212981
DOI: 10.1111/j.1749-6632.1977.tb21970.x -
Haematologica Mar 2000Conventional myeloablative conditioning regimens for allografting rely on the use of toxic myeloablative and immunosuppressive therapies to achieve engraftment and... (Review)
Review
Conventional myeloablative conditioning regimens for allografting rely on the use of toxic myeloablative and immunosuppressive therapies to achieve engraftment and control of hematologic neoplasias. Unfortunately, these regimens have resulted in substantial morbidity and mortality. Preclinical and pilot clinical studies have shown that conditioning regimens can be reduced in intensity (resulting in reduced morbidity and mortality) since stem cell allografts can create their own space in the host's bone marrow. Initial promising results with these attenuated conditioning regimens confirm that such an approach is feasible in patients with hematologic neoplasias and genetic diseases ineligible for conventional allografting because of age and/or organ toxicity. The combination of high-dose therapy/autografting followed by a low intensity conditioning regimen (Flu-Cy protocol) and donor mobilized hematopoietic stem cell infusion (mini-allografting) may ultimately be useful in advanced resistant hematologic neoplasia. Finally, these initial promising results with attenuated conditioning regimens have been achieved in transplants with HLA-identical siblings. In the future the main goal will be to explore non-toxic conditioning regimens in the context of transplants from related MHC-mismatched or unrelated MHC-matched donors by increasing the patient's immunosuppression.
Topics: Antineoplastic Agents; Graft vs Host Disease; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Pilot Projects; Transplantation Conditioning; Transplantation, Homologous; Vidarabine
PubMed: 10702821
DOI: No ID Found -
Journal of Pharmaceutical Sciences Jul 1980The mathematical problem of simultaneous transport and metabolism in the case of nonuniform enzyme distributions in the skin was solved, and the solutions were used for...
Physical model evaluation of topical prodrug delivery--simultaneous transport and bioconversion of vidarabine-5'-valerate V: Mechanistic analysis of influence of nonhomogeneous enzyme distributions in hairless mouse skin.
The mathematical problem of simultaneous transport and metabolism in the case of nonuniform enzyme distributions in the skin was solved, and the solutions were used for analyzing experimental data. Experimental data were obtained from permeation experiments with 3H-vidarabine and its 5'-valerate using cellophane tape-stripped hairless mouse skin. Results of the analyses revealed that the esterase activity was four to nine times higher in the epidermis than in the dermis, whereas the deaminase activity was about the same in the two strata. These results were in good agreement with independent experiments using tissue homogenates. The enzyme distributions and the previously reported diffusivities were employed in generating concentration profiles for the prodrug and the drug in the skin. These results may be used in predicting the possible therapeutic effect of the prodrug when it is topically applied.
Topics: Administration, Topical; Animals; Biotransformation; Diffusion; Mice; Mice, Nude; Models, Biological; Skin; Vidarabine
PubMed: 7391938
DOI: 10.1002/jps.2600690708 -
Clinical Oncology (Royal College of... 1996Three analogues of the purine 2-deoxyadenosine are available for the treatment of low grade lymphoproliferative disorders: pentostatin, cladribine and fludarabine. They... (Review)
Review
Three analogues of the purine 2-deoxyadenosine are available for the treatment of low grade lymphoproliferative disorders: pentostatin, cladribine and fludarabine. They have some common features in their mode of action, but differ both in their detailed pharmacology and the extent to which they have activity against specific lymphoid malignancies. Studies defining the scope of these drugs as single agents are now being followed by plans to exploit their potential synergy with other agents and clinically to define useful combination therapies.
Topics: Antineoplastic Agents; Cladribine; Humans; Lymphoproliferative Disorders; Pentostatin; Vidarabine
PubMed: 8934048
DOI: 10.1016/s0936-6555(05)80714-9 -
Annals of Ophthalmology Jul 1977
Clinical Trial Comparative Study
Topics: Animals; Clinical Trials as Topic; Cornea; Cricetinae; DNA Replication; Humans; Idoxuridine; Keratitis, Dendritic; Rabbits; Vidarabine; Visual Acuity; Wound Healing
PubMed: 332031
DOI: No ID Found