title: Phase II trial of arsenic trioxide in relapsed and refractory acute myeloid leukemia, secondary leukemia and/or newly diagnosed patients at least 65 years old.
abstract: The prognosis for patients with relapsed/refractory AML, secondary leukemia and AML in older adults is extremely poor. An appealing alternative approach to intensive cytotoxic chemotherapy is to induce apoptosis with a novel agent. There is in vitro evidence that arsenic trioxide (ATO) has anti-proliferative and pro-apoptotic effects on myeloid leukemia cell lines. To evaluate efficacy and toxicities of ATO, we conducted a phase II trial including subjects with relapsed/refractory or secondary AML or age > or = 65 years with de novo disease. Eleven subjects were entered with a median age of 77 years (56-90) and a median total dose of ATO of 415.55 mg (91.5-793) with a daily dose of 0.25 mg/kg. Median survival following the first dose of ATO was 2.25 months (0.4-19). Myelosuppression was the major adverse effect, most likely due to disease progression rather than drug-related. All subjects had progressive disease. There was no direct treatment-related mortality. Based on this study, we do not recommend single agent ATO as a treatment option for AML.
authors.affiliation: Division of Hematology-Oncology, Northwestern University, Feinberg School of Medicine, Robert H Lurie Comprehensive Cancer Center, 676 N St. Clair Street, Suite 850, Chicago, IL 60611, USA.
authors.forename: Simrit
authors.initials: S
authors.lastname: Parmar
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Rundhaugen
authors.forename: Larry
authors.initials: L
authors.lastname: Boehlke
authors.forename: MaryBeth
authors.initials: M
authors.lastname: Riley
authors.forename: Chadi
authors.initials: C
authors.lastname: Nabhan
authors.forename: Adekunle
authors.initials: A
authors.lastname: Raji
authors.forename: John L
authors.initials: JL
authors.lastname: Frater
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage*; D001856:Bone Marrow Examination; D018450:Disease Progression; D018432:Drug Resistance, Multiple; D005260:Female; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000188:drug therapy; D010087:Oxides / Q000008:administration & dosage* / Q000633:toxicity; D016879:Salvage Therapy / Q000379:methods; D016896:Treatment Outcome
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D001152:Arsenicals; D006023:Glycoproteins; D010087:Oxides; D000077237:Arsenic Trioxide