title: Oral tetra-arsenic tetra-sulfide formula versus intravenous arsenic trioxide as first-line treatment of acute promyelocytic leukemia: a multicenter randomized controlled trial.
abstract: OBJECTIVE
  This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of an oral tetra-arsenic tetra-sulfide (As4S4) -containing formula named the Realgar-Indigo naturalis formula (RIF) compared with intravenous arsenic trioxide (ATO) as both induction and maintenance therapies for newly diagnosed acute promyelocytic leukemia (APL).
  
  
  METHODS
  In all, 242 patients with APL were randomly assigned (1:1) to oral RIF (60 mg/kg) or ATO (0.16 mg/kg) combined with all-trans retinoic acid (ATRA; 25 mg/m(2)) during induction therapy. After achieving complete remission (CR), all patients received three courses of consolidation chemotherapy and maintenance treatment with sequential ATRA followed by either RIF or ATO for 2 years. The primary end point was the rate of disease-free survival (DFS) at 2 years, which was assessed for noninferiority with a 10% noninferiority margin.
  
  
  RESULTS
  The median follow-up time was 39 months. DFS at 2 years was 98.1% (106 of 108) in the RIF group and 95.5% (107 of 112) in the ATO group. The DFS difference was 2.6% (95% CI, -3.0% to 8.0%). The lower limit of the 95% CI of DFS difference was greater than the -10% noninferiority margin, confirming noninferiority (P < .001). No significant differences were noted between the RIF and ATO groups with regard to the CR rate (99.1% v 97.2%; P = .62) or the overall survival at 3 years (99.1% v 96.6%; P = .18). The rates of adverse events were similar in the two groups.
  
  
  CONCLUSIONS
  Oral RIF plus ATRA is not inferior to intravenous ATO plus ATRA as first-line treatment of APL and may be considered as a routine treatment option for appropriate patients.
authors.affiliation: Hong-Hu Zhu, Hao Jiang, and Xiao-Jun Huang, Peking University People's Hospital, Beijing; De-Pei Wu, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu; Jie Jin, First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang; Jian-Yong Li, First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing; Jun Ma, Harbin Institute of Hematology and Oncology, Harbin; Jian-Xiang Wang, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin; and Sai-Juan Chen, Rui Jin Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Hong-Hu
authors.initials: HH
authors.lastname: Zhu
authors.forename: De-Pei
authors.initials: DP
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Jian-Xiang
authors.initials: JX
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.forename: Sai-Juan
authors.initials: SJ
authors.lastname: Chen
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Huang
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005334:Fever / Q000139:chemically induced; D005500:Follow-Up Studies; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D060046:Maintenance Chemotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D013440:Sulfides / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D001152:Arsenicals; D004365:Drugs, Chinese Herbal; D010087:Oxides; D013440:Sulfides; C528183:realgar-indigo naturalis; D014212:Tretinoin; D000077237:Arsenic Trioxide; C534735:tetraarsenic tetrasulfide