Older and New Formulations of Cladribine. Pharmacology and Clinical Efficacy in Hematological Malignancies

Robak, Tadeusz; Korycka, Anna; Robak, Ewa

doi:10.2174/157489206775246467

Cited by 12 publications

(4 citation statements)

References 129 publications

(186 reference statements)

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“…The mechanisms of cladribine activity are based on inhibition of enzymes involved in DNA, RNA, and protein synthesis. Cytotoxicity of CdA is associated with events critical to cell entry into S phase (BEUTLER 1992;ROBAK et al 2006aROBAK et al , 2006b). …”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

In vitro Response of Human Pathological Hematopoietic Cells to Cladribine

Mazur

Opydo-Chanek²,

Stojak³

et al. 2013

folia biol (krakow)

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Section: Resultsmentioning

confidence: 99%

“…Cladribine has established clinical activity in hematological malignancies (DELANNOY 1996;ROBAK 2003;PARKER et al 2004;GREYZ & SAVEN 2004;ROBAK et al 2005ROBAK et al , 2006aROBAK et al , 2006bROBAK et al , 2006c. Nevertheless, some aspects of the action of cladribine are as yet unclear.…”

mentioning

confidence: 99%

In vitro Response of Human Pathological Hematopoietic Cells to Cladribine

Mazur

Opydo-Chanek²,

Stojak³

et al. 2013

folia biol (krakow)

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“…Finally, the presence of lymphopaenia and biological liver alterations is important to consider in patients who will eventually need treatment for their disease. In particular, cladribine, a promising treatment for progressive PLCH [ 27 , 28 ], is known to induce deep and prolonged lymphopaenia and hepatic side effects [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Extrathoracic investigation in adult patients with isolated pulmonary langerhans cell histiocytosis

Tazi

Margerie-Mellon

Vercellino

et al. 2016

Orphanet J Rare Dis

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BackgroundAn important objective on diagnosis of patients with Langerhans cell histiocytosis (LCH) is to determine the extent of disease. However, whether systematic extrathoracic investigation is needed in adult patients with clinically isolated pulmonary LCH (PLCH) has not been evaluated.MethodsIn this prospective, multicentre study, 54 consecutive patients with newly diagnosed clinically isolated PLCH were systematically evaluated at inclusion by bone imaging and blood laboratory testing to search for subclinical extrapulmonary LCH involvement. The patients were followed over a 2-year period. At each visit, they were asked about the presence of extrapulmonary manifestations of LCH.ResultsIn the absence of bone symptoms, the skeletal X-ray survey results were normal for all but two patients who had a localised bone lesion consistent with possible LCH involvement, that remained unchanged over 2 years of follow-up. Whole-body bone scintigraphy did not add information to the plain radiography findings for the detection of asymptomatic bone involvement in isolated PLCH. Conversely, it showed nonspecific focal bone uptake in 18 % of the patients, mainly corresponding to post-traumatic or degenerative abnormalities unrelated to LCH. Mild leucocytosis due to neutrophilia was observed in 22 % of the patients and was not related to their smoking habits. Three patients had mild isolated lymphocytosis without haematological disease, whereas two patients had mild lymphopaenia. A mild inflammatory biological syndrome was observed in a minority of patients without infection or constitutional symptoms and was not associated with progressive disease. A substantial proportion (24.5 %) of the patients had abnormal biological liver test results, including elevated liver enzymes and/or cholestasis, which were not linked to LCH involvement in this cohort.ConclusionsObtaining a thorough history and performing comprehensive physical examination are essential for staging patients diagnosed with PLCH. In the absence of symptoms or signs suggestive of extrapulmonary LCH involvement, the systematic performing of recommended bone imaging does not appear informative. Although the observed blood laboratory abnormalities were not specifically related to LCH, performing these tests in the diagnostic workup for PLCH is useful because some of these alterations may impact patient management.Trial registrationClinicalTrials.gov: No. NCT01225601; URL: www.clinicaltrials.gov

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“…However, oral administration of 2-CdA solution induces degradation to 2-chloroadenine, which can be overcome by doubling the dose. The bioavailability after oral administration of 2-CdA is 35-55% [ 60 ]. Maximum oral bioavailability after the dose of 0.18 mg/day dissolved in phosphate buffer solution is 55% [ 54 ].…”

Section: Pharmacology and Mechanism Of Actionmentioning

confidence: 99%

Current Status of Older and New Purine Nucleoside Analogues in the Treatment of Lymphoproliferative Diseases

et al. 2009

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For the past few years more and more new cytotoxic agents active in the treatment of hematological malignancies have been synthesized and become available for either in vitro studies or clinical trials. Among them the class of antineoplastic drugs belonging to the purine nucleoside analogues group (PNAs) plays an important role. Three of them: pentostatin (DCF), cladribine (2-CdA) and fludarabine (FA) were approved by Food and Drug Administration (FDA) for the treatment of hematological malignancies. Recently three novel PNAs: clofarabine (CAFdA), nelarabine (ara-G) and forodesine (immucillin H, BCX-1777) have been synthesized and introduced into preclinical studies and clinical trials. These agents seem to be useful mainly for the treatment of human T-cell proliferative disorders and they are currently undergoing clinical trials in lymphoid malignancies. However, there are also several studies suggesting the role of these drugs in B-cell malignancies. This review will summarize current knowledge concerning the mechanism of action, pharmacologic properties, clinical activity and toxicity of PNAs accepted for use in clinical practice, as well as new agents available for clinical trials.

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Older and New Formulations of Cladribine. Pharmacology and Clinical Efficacy in Hematological Malignancies

Cited by 12 publications

References 129 publications

In vitro Response of Human Pathological Hematopoietic Cells to Cladribine

In vitro Response of Human Pathological Hematopoietic Cells to Cladribine

Extrathoracic investigation in adult patients with isolated pulmonary langerhans cell histiocytosis

Current Status of Older and New Purine Nucleoside Analogues in the Treatment of Lymphoproliferative Diseases

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