title: Phase I trials of amonafide as monotherapy and in combination with cytarabine in patients with poor-risk acute myeloid leukemia.
abstract: Amonafide-l-malate (amonafide) is a unique DNA intercalator that maintains activity in the presence of MDR mechanisms, a frequent cause of treatment-failure in secondary AML. 43 patients with relapsed/refractory or secondary AML or CML blast crisis were enrolled into two phase I dose-escalation studies investigating amonafide as monotherapy or in combination with cytarabine. 3/17 patients in the monotherapy trial and 10/26 patients in the combination trial achieved a complete remission. Between both trials responses occurred in 9/20 patients with secondary AML. Both trials demonstrated an acceptable safety profile and significant antileukemic activity in patients with poor-risk AML, especially those with secondary AML.
authors.affiliation: North Shore University Hospital, Albert Einstein College of Medicine, Monter Cancer Center, 450 Lakeville Road, Lake Success, NY 11042, United States. allen@nshs.edu
authors.forename: Steven L
authors.initials: SL
authors.lastname: Allen
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kolitz
authors.forename: Ante S
authors.initials: AS
authors.lastname: Lundberg
authors.forename: John M
authors.initials: JM
authors.lastname: Bennett
authors.forename: Robert L
authors.initials: RL
authors.lastname: Capizzi
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Budman
mesh_terms: D000225:Adenine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D053644:Naphthalimides / Q000008:administration & dosage* / Q000009:adverse effects; D063065:Organophosphonates; D012074:Remission Induction; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D053644:Naphthalimides; D063065:Organophosphonates; D003561:Cytarabine; C037020:amonafide; D000225:Adenine