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RAPID COMMUNICATION
Treatment With a New Synthetic Retinoid, Am80, of Acute Promyelocytic Leukemia Relapsed From Complete Remission Induced by All-trans Retinoic Acid
Tadasu Tobita,
Akihiro Takeshita,
Kunio Kitamura,
Kazunori Ohnishi,
Mitsuaki Yanagi,
Akira Hiraoka,
Takahiro Karasuno,
Makoto Takeuchi,
Shuuichi Miyawaki,
Ryuzo Ueda,
Tomoki Naoe, and
Ryuzo Ohno
From the Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu; the Department of Infectious Diseases, Nagoya University School of Medicine, Nagoya; the Department of Medicine, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka; the Department of Medicine, National Minami-Okayama Hospital, Okayama; the Department of Medicine, Saiseikai Maebashi Hospital, Maebashi; and the Department of Medicine, Nagoya City University School of Medicine, Nagoya, Japan.
Differentiation therapy with all-trans retinoic acid (ATRA) has marked a major advance and become the first choice drug in the treatment of acute promyelocytic leukemia (APL). However, patients who relapse from ATRA-induced complete remission (CR) have difficulty in obtaining a second CR with a second course of ATRA therapy alone. We tested the efficacy of a new synthetic retinoid, Am80, in APL that had relapsed from CR induced by ATRA in a prospective multicenter study. Am80 is approximately 10 times more potent than ATRA as an in vitro differentiation inducer, is more stable to light, heat, and oxidation than ATRA, has a low affinity for cellular retinoic acid binding protein, and does not bind to retinoic acid receptor- . Patients received Am80, 6 mg/m2, orally alone daily until CR. Of 24 evaluable patients, 14 (58%) achieved CR. The interval from the last ATRA therapy was not different between CR and failure cases. The clinical response was well correlated with the in vitro response to Am80 in patients examined. Adverse events included 1 retinoic acid syndrome, 1 hyperleukocytosis, 9 xerosis, 8 cheilitis, 16 hypertriglyceridemia, and 15 hypercholesterolemia, but generally milder than those of ATRA, which all patients had received previously. Am80 is effective in APL relapsed from ATRA-induced CR and deserves further trials, especially in combination with chemotherapy.
Blood, Vol. 90 No. 3 (August 1), 1997:
pp. 967-973
© 1997 by The American Society of Hematology.
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