Treatment with a new synthetic retinoid, Am80, of acute promyelocytic leukemia relapsed from complete remission induced by all-trans retinoic acid.
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-gamma. 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.
Tobita
T
T
Department of Medicine, Hamamatsu University School of Medicine, Handa-cho, Japan.
Takeshita
A
A
Kitamura
K
K
Ohnishi
K
K
Yanagi
M
M
Hiraoka
A
A
Karasuno
T
T
Takeuchi
M
M
Miyawaki
S
S
Ueda
R
R
Naoe
T
T
Ohno
R
R
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001565:Benzoates / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003630:Daunorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D007964:Leukocytosis / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced; D011446:Prospective Studies; D018168:Receptors, Retinoic Acid / Q000187:drug effects; D012008:Recurrence; D012074:Remission Induction; D012176:Retinoids / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016879:Salvage Therapy; D013764:Tetrahydronaphthalenes / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000097768:Retinoic Acid Receptor gamma
D000970:Antineoplastic Agents; D001565:Benzoates; D003561:Cytarabine; D003630:Daunorubicin; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D013764:Tetrahydronaphthalenes; D014212:Tretinoin; D000097768:Retinoic Acid Receptor gamma; C061133:tamibarotene