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Blood, 25 June 2009, Vol. 113, No. 26, pp. 6528-6532. Prepublished online as a Blood First Edition Paper on May 1, 2009; DOI 10.1182/blood-2009-03-211821.
CLINICAL TRIALS AND OBSERVATIONS Phase 2 study of the efficacy and safety of the combination of arsenic trioxide, interferon alpha, and zidovudine in newly diagnosed chronic adult T-cell leukemia/lymphoma (ATL)1 Immunology Research Centre Bu-Ali Research Institute, 2 Department of Pathology and Laboratory Medicine, and 3 Department of Internal Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; 4 Department of Internal Medicine, American University of Beirut, Beirut, Lebanon; 5 Oncovirologie et Biothérapies, Centre National de la Recherche Scientifique (CNRS) FRE 3011, Université Claude Bernard, Centre Léon Bérard, Hopital Edouard Herriot, Lyon, France; 6 Department of Dermatology, and 7 Microbiology and Virology Research Center, Bu-Ali Research institute, Mashhad University of Medical Sciences, Mashhad, Iran; 8 Department of Pharmaceutical Biotechnology, College of Pharmacy, Tehran University of Medical Science, Tehran, Iran; 9 CNRS Unité Mixte de Recherche (UMR) 7151, Laboratoire Associé au Comité de Paris de la Ligue contre le Cancer, Paris, France; and 10 CNRS UMR 8603 and Department of Hematology, Necker Hospital, Paris, France
Adult T-cell leukemia/lymphoma (ATL) is resistant to chemotherapy and carries a dismal prognosis particularly for the acute and lymphoma subtypes. Promising results were obtained with the combination of zidovudine and interferon-alpha. Chronic ATL has a relatively better outcome, but poor long-term survival is noted when patients are managed with a watchful-waiting policy or with chemotherapy. In ATL cell lines, arsenic trioxide shuts off constitutive NF-
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| Copyright © 2009 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
B activation and potentiates interferon-alpha apoptotic effects through proteasomal degradation of Tax. Clinically, arsenic/interferon therapy exhibits some efficacy in refractory aggressive ATL patients. These results prompted us to investigate the efficacy and safety of the combination of arsenic, interferon-alpha, and zidovudine in 10 newly diagnosed chronic ATL patients. An impressive 100% response rate was observed including 7 complete remissions, 2 complete remissions but with more than 5% circulating atypical lymphocytes, and 1 partial response. Responses were rapid and no relapse was noted. Side effects were moderate and mostly hematologic. In conclusion, treatment of chronic ATL with arsenic, interferon-alpha, and zidovudine is feasible and exhibits an impressive response rate with moderate toxicity. Long-term follow up will clarify whether this will translate to disease cure. Overall, these clinical results strengthen the concept of oncogene-targeted cancer therapy. 
