Successful Treatment of Relapse of Acute Promyelocytic Leukemia with a New Synthetic Retinoid, Am80
Authors: Akihiro Takeshita
Journal: Annals of Internal Medicine (1996)

Brief Reports15 May 1996Successful Treatment of Relapse of Acute Promyelocytic Leukemia with a New Synthetic Retinoid, Am80Akihiro Takeshita, MD, Yukiko Shibata, MD, Kaori Shinjo, MD, Mitsuaki Yanagi, MD, Tadasu Tobita, MD, Kazunori Ohnishi, MD, Shuichi Miyawaki, MD, Koichi Shudo, PhD, and Ryuzo Ohno, MDAkihiro Takeshita, MD, Yukiko Shibata, MD, Kaori Shinjo, MD, Mitsuaki Yanagi, MD, Tadasu Tobita, MD, Kazunori Ohnishi, MD, Shuichi Miyawaki, MD, Koichi Shudo, PhD, and Ryuzo Ohno, MDAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-124-10-199605150-00006 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail All-trans retinoic acid (ATRA) has proven to be a major advance in the management of patients with acute promyelocytic leukemia. Several studies [1-5] have shown that a treatment program using ATRA for induction followed by several cycles of cytotoxic chemotherapy for consolidation yields overall survival rates superior to those produced by chemotherapy alone. Nonetheless, ATRA has several important limitations, one of which is the rapid development of resistance to it by patients [6]. We report here, for the first time, that the new synthetic retinoid Am80 (4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl) carbamoyl] benzoic acid) (Figure 1) [7, 8] induced complete remission without serious adverse ...References1. Huang ME, Ye YC, Chen SR, Chai JR, Lu MX, Zhoa L, et al. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988; 72:567-72. Google Scholar2. Warrell RP Jr, Frankel SR, Miller WH Jr, Scheinberg DA, Itri LM, Hittelman WN, et al. Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). N Engl J Med. 1991; 324:1385-93. Google Scholar3. Ohno R, Ohnishi K, Takeshita A, Tanimoto M, Murakami H, Kanamaru A, et al. All-trans retinoic acid therapy in relapsed/refractory or newly diagnosed acute promyelocytic leukemia (APL) in Japan. Leukemia. 1994; 8(Suppl 3):S64-9. Google Scholar4. Kanamaru A, Takemoto Y, Tanimoto M, Murakami H, Asou N, Kobayashi T, et al. All-trans retinoic acid for the treatment of newly diagnosed acute promyelocytic leukemia. Japan Adult Leukemia Study Group. Blood. 1996; 85:1202-6. Google Scholar5. Warrell RP Jr, de The H, Wang ZY, Degos L. Acute promyelocytic leukemia. N Engl J Med. 1993; 329:177-89. Google Scholar6. Degos L, Dombret H, Chomienne C, Daniel MT, Miclea JM, Chastang C, et al. All-trans-retinoic acid as a differentiating agent in the treatment of acute promyelocytic leukemia. Blood. 1995; 85:2643-53. Google Scholar7. Kagechika H, Kawachi E, Hashimoto Y, Himi T, Shudo K. Retinobenzoic acids. 1. Structure-activity relationships of aromatic amides with retinoidal activity. J Med Chem. 1988; 31:2182-92. Google Scholar8. Hashimoto Y, Kagechica H, Kawaguchi E, Fukazawa H, Shudo K. Correlation of differentiation-inducing activity of retinoids on human leukemia cell lines HL-60 and NB4. J Cancer Res Clin Oncol. 1995; 121:696-8. Google Scholar9. Yamada O, Hatake K, Tanimoto M, Ishiyama T, Ohno R, Shirakawa S, et al. [Co-operative study of all-trans retinoic acid as a differentiation induction therapy of acute promyelocytic leukemia]. Gan To Kagaku Ryoho. 1994; 21:1981-9 Google Scholar10. Cornic M, Delva L, Castaigne S, Lefebvre P, Balitrand N, Degos L, et al. In vitro all-trans retinoic acid (ATRA) sensitivity and cellular retinoic acid binding protein (CRABP) levels in relapse leukemic cells after remission induction by ATRA in acute promyelocytic leukemia. Leukemia. 1994; 8:914-7. Google Scholar11. Muindi J, Frankel SR, Miller WH Jr, Jakubowski A, Scheinberg DA, Young CW, et al. Continuous treatment with all-trans retinoic acid causes a progressive reduction in plasma drug concentrations: implications for relapse and retinoid resistance in patients with acute promyelocytic leukemia. Blood. 1992; 79:299-303. Google Scholar12. Miller WH Jr, Jakubowski A, Tong WP, Miller VA, Rigas JR, Benedetti F, et al. 9-cis retinoic acid induces complete remission but does not reverse clinically acquired retinoid resistance in acute promyelocytic leukemia. Blood. 1995; 85:3021-7. Google Scholar13. Zelent A, Krust A, Petkovich M, Kastner P, Chambon P. Cloning of murine α and β retinoic acid receptors and a novel receptor γ predominantly expressed in skin. Nature. 1989; 339:714-7. 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