title: Arsenic trioxide therapy in relapsed or refractory Japanese patients with acute promyelocytic leukemia: updated outcomes of the phase II study and postremission therapies.
abstract: Recently, arsenic trioxide (ATO) has been proved to induce complete remission (CR) at a high rate in patients with acute promyelocytic leukemia (APL). We prospectively investigated the safety and efficacy of ATO therapy in patients with relapsed and refractory APL and examined the duration of CR and the postremission therapies. Initially, 0.15 mg/kg ATO was administered until bone marrow remission to a maximum of 60 days. After the patient achieved CR, 1 additional ATO course at the same dosage was administered for 25 days. Of 34 patients, 31 (91%) achieved CR. PML-RAR3 messenger RNA was not detected in the bone marrow of 18 (72%) of the 25 patients evaluated by reverse transcriptase-polymerase chain reaction analysis. At a median follow-up of 30 months, the estimated 2-year overall survival rate was 56%, and the estimated 2-year event-free survival rate was 17%. During the ATO therapy, QTc prolongation was observed in most cases. Fifteen patients developed ventricular tachycardia, and 1 of them showed torsades de pointes. Other adverse events were nausea, water retention, APL differentiation syndrome, skin eruption, liver dysfunction, and peripheral neuropathy, all of which were quite tolerable. ATO therapy was remarkably effective for relapsed APL; however, postremission therapies were necessary to maintain a durable remission.
authors.affiliation: Department of Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Japan. shigeno@hama-med.ac.jp
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Shigeno
authors.forename: Kensuke
authors.initials: K
authors.lastname: Naito
authors.forename: Naohi
authors.initials: N
authors.lastname: Sahara
authors.forename: Miki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Satoki
authors.initials: S
authors.lastname: Nakamura
authors.forename: Sinya
authors.initials: S
authors.lastname: Fujisawa
authors.forename: Kaori
authors.initials: K
authors.lastname: Shinjo
authors.forename: Akihiro
authors.initials: A
authors.lastname: Takeshita
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ohno
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ohnishi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage* / Q000009:adverse effects; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D006801:Humans; D007564:Japan; D015473:Leukemia, Promyelocytic, Acute / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis; D010087:Oxides / Q000008:administration & dosage* / Q000009:adverse effects; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D010087:Oxides; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D000077237:Arsenic Trioxide