title: Treatment of newly diagnosed and relapsed acute promyelocytic leukemia with intravenous liposomal all-trans retinoic acid.
abstract: A novel intravenous liposomal formulation of all-trans retinoic acid (ATRA) was evaluated in 69 patients with acute promyelocytic leukemia (APL): 32 new diagnoses, 35 relapses, and 2 oral ATRA failures. Liposomal ATRA (90 mg/m(2)) was administered every other day until complete remission (CR) or a maximum of 56 days. Treatment following CR was liposomal ATRA with or without chemotherapy. In an intent-to-treat (ITT) analysis of all patients, CR rates were 62%, 70%, and 20% in newly diagnosed, group 1 first relapses (ATRA naive or off oral ATRA more than or equal to 1 year), or group 2 relapses (second or subsequent relapse or first relapses off oral ATRA less than 1 year), respectively. In 56 evaluable patients (receiving 4 or more doses), CR rates for the same groups were 87% (20 of 23), 78% (14 of 18), and 23% (3 of 13). Remission failure in newly diagnosed patients was not from resistant disease. Several patients in CR became polymerase chain reaction (PCR) negative for promyelocytic leukemia/retinoic acid receptor-alpha (PML/RARalpha) after liposomal ATRA alone. Toxicity was generally mild, most commonly headaches (67. 5%). Eighteen patients (26%) had ATRA syndrome develop during induction. One-year survival of ITT patients was 62%, 56%, and 20% for newly diagnosed, group 1, and group 2, respectively. The medium duration of CR has not yet been reached and was 18 and 5.5 months in the same groups. These results demonstrate that liposomal ATRA is effective in inducing CR in newly diagnosed or group 1 APL patients. It provides a reliable dosage of ATRA for patients with APL unable to swallow or absorb medications and can induce molecular remissions without chemotherapy.
authors.affiliation: Division of Hematology, University of Southern California Medical School and Norris Cancer Center, Los Angeles, CA, USA. douer_d@mikey.hsc.usc.edu
authors.forename: D
authors.initials: D
authors.lastname: Douer
authors.forename: E
authors.initials: E
authors.lastname: Estey
authors.forename: S
authors.initials: S
authors.lastname: Santillana
authors.forename: J M
authors.initials: JM
authors.lastname: Bennett
authors.forename: G
authors.initials: G
authors.lastname: Lopez-Bernstein
authors.forename: K
authors.initials: K
authors.lastname: Boehm
authors.forename: T
authors.initials: T
authors.lastname: Williams
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000378:metabolism; D018572:Disease-Free Survival; D004339:Drug Compounding / Q000592:standards; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D015473:Leukemia, Promyelocytic, Acute / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D008081:Liposomes / Q000008:administration & dosage* / Q000592:standards; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011446:Prospective Studies; D044469:Racial Groups; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage* / Q000633:toxicity*
chemical_list: D008081:Liposomes; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin; D004247:DNA