Oral Tetra-Arsenic Tetra-Sulfide Formula Versus Intravenous Arsenic Trioxide As First-Line Treatment of Acute Promyelocytic Leukemia: A Multicenter Randomized Controlled Trial

• Published in: Journal of clinical oncology Vol. 31; no. 33; pp. 4215 - 4221
• Main Authors: Zhu, Hong-Hu, Wu, De-Pei, Jin, Jie, Li, Jian-Yong, Ma, Jun, Wang, Jian-Xiang, Jiang, Hao, Chen, Sai-Juan, Huang, Xiao-Jun
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 20.11.2013
• Subjects: Administration, Intravenous; Administration, Oral; Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Arsenicals - administration & dosage; Arsenicals - adverse effects; Arsenicals - therapeutic use; Biological and medical sciences; Disease-Free Survival; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - therapeutic use; Female; Fever - chemically induced; Follow-Up Studies; Hematologic and hematopoietic diseases; Humans; Induction Chemotherapy - methods; Leukemia, Promyelocytic, Acute - drug therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Liver - drug effects; Liver - pathology; Maintenance Chemotherapy - methods; Male; Medical sciences; Middle Aged; Oxides - administration & dosage; Oxides - adverse effects; Oxides - therapeutic use; Remission Induction; Sulfides - administration & dosage; Sulfides - therapeutic use; Treatment Outcome; Tretinoin - administration & dosage; Tretinoin - therapeutic use; Tumors; Young Adult; Promyelocytic leukemia; Intravenous administration; Arsenic; Acute; Multicenter study; Arsenic trioxide; Malignant hemopathy; Randomized controlled trial; First line treatment; Carcinogen; Sulfides; Cancerology; Comparative study; Cancer; M3 acute myelocytic leukemia
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2013.48.8312

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). 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. 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. 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.