Tamibarotene for the treatment of acute promyelocytic leukemia. (September 2014)

• Record Type: Journal Article
• Authors: Takeshita, Akihiro; Shinagawa, Katsuji; Adachi, Miwa; Ono, Takaaki; Kiguchi, Toru; Naoe, Tomoki
• Is Part Of: Expert opinion on orphan drugs. Volume 2:Number 9(2014:Sep.)
• Page Start: 961
• Page End: 969
• Publication Date: 2014-09
• Subjects: Orphan drugs -- Periodicals; Rare diseases -- Periodicals; Chemotherapy -- Periodicals; 615.1
• DOI: 10.1517/21678707.2014.943733
• Languages: English
• ISSNs: 2167-8707

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold> <italic>Introduction:</italic> </bold> Acute promyelocytic leukemia (APL) is characterized by a reciprocal translocation between chromosomes 15 and 17 yielding the <italic>PML-RARA</italic> fusion gene, which deregulates cell proliferation and blocks granulocyte differentiation. All-<italic>trans</italic> retinoic acid (ATRA) dramatically improved the prognosis of APL, but relatively, small number of relapsing patients achieves second remission with ATRA alone.</p> <p> <bold> <italic>Areas covered:</italic> </bold> <ext-link ext-link-type="uri" xlink:href="http://informahealthcare.com/action/doSearch?type=advanced&displaySummary=true&displaySummary=true&field1=keywords&text1=Tamibarotene&logicalOpe1=OR&field2=articletitle&text2=Tamibarotene&logicalOpe2=AND&field3=all&text3=&search=Search&categoryId=41010274&categoryId=40002416&categoryId=40004717&categoryId=40004717&filter=multiple&AfterMonth=1&AfterYear=&BeforeMonth=12&BeforeYear=&sortBy=date&nh=20" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">Tamibarotene</ext-link>, a new synthetic retinoid, is about 10 times more potent than ATRA, chemically more stable than ATRA, with low affinity for cellular RA-binding protein and no detectable binding to RA receptor-γ. Tamibarotene has a significant effect on ATRA-resistant APLs. Some arsenic trioxide (ATO) and gemtuzumab ozogamicin-resistant APLs are reportedly tamibarotene<bold>-</bold>sensitive.</p> <p> <bold> <italic>Expert opinion:</italic> </bold> Tamibarotene was tested in APL-relapsed patients after ATRA-induced complete remission (CR), and 14/24 patients (58%) achieved CR. In an independent trial, 24/39 (61.5%) APL patients achieved CR including 5 newly diagnosed patients and 13 patients who had relapsed twice or more. A prospective randomized study compared tamibarotene with ATRA as maintenance therapy. Four-year relapse-free survival rate was 84% (ATRA) and 91% (tamibarotene) (p = 0.095). In high-risk patients, this became significant (58% ATRA, 87% tamibarotene, p = 0.028). These results suggest tamibarotene should be tested in induction or consolidation therapy and in combination with ATO.</p> </abstract>