T. Tobita et al., TREATMENT WITH A NEW SYNTHETIC RETINOID, AM80, OF ACUTE PROMYELOCYTICLEUKEMIA RELAPSED FROM COMPLETE REMISSION INDUCED BY ALL-TRANS-RETINOIC ACID, Blood, 90(3), 1997, pp. 967-973
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 s
econd CR with a second course of ATRA therapy alone. We tested the eff
icacy of a new synthetic retinoid, Am80, in APL that had relapsed from
CR induced by ATRA in a prospective multicenter study. Am80 is approx
imately 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/m(
2), orally alone daily until CR. Of 24 evaluable patients, 14 (58%) ac
hieved CR. The interval from the last ATRA therapy was not different b
etween CR and failure cases. The clinical response was well correlated
with the in vitro response to Am80 in patients examined. Adverse even
ts 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.
(C) 1997 by The American Society of Hematology.