[Clinical experience with a new synthetic retinoid, tamibarotene (Am-80) for relapsed or refractory acute promyelocytic leukemia].
A new synthetic retinoid, Am-80 is expected to overcome all-trans retinoic acid (ATRA) resistance, because of several times more potent differentiation activity than ATRA and sustained plasma level during continuous administration due to a lower affinity for cellular retinoic acid binding protein. In a preliminary study in Japan, 14 (58%) of 24 acute promyelocytic leukemia (APL) patients who had relapsed from ATRA induced complete remission (CR) achieved a second CR. Of these 14 CR patients, 4 of 6 who underwent allogeneic stem cell transplantation (SCT) are alive, and 4 of 8 patients who received only chemotherapy are alive without relapse for >4 years. Adverse events include xerosis, cheilitis, hyperlipidemia and so on, but these were generally milder than ATRA. In a phase 2 clinical trial, 25 (61%) of 41 patients entered CR. Among 23 first relapsed patients, 18 (78.3%) patients entered CR, indicating excellent salvage effects for ATRA-relapsed patients. Am-80 may improve disease free survival when used as remission induction and/or maintenance therapy, and it may be effective for relapse from ATRA-induced remission and be curative for patients who receive SCT or intensive post remission chemotherapy.
Division of Hematology, National Hospital Organization Minami-Okayama Medical Center.
Makoto
M
Takeuchi
D001565:Benzoates / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D017322:Clinical Trials, Phase II as Topic; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D010865:Pilot Projects; D012008:Recurrence; D012074:Remission Induction; D012176:Retinoids; D013764:Tetrahydronaphthalenes / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
D001565:Benzoates; D012176:Retinoids; D013764:Tetrahydronaphthalenes; C061133:tamibarotene