|Oral Tetra-Arsenic Tetra-Sulfide Formula Versus Intravenous Arsenic Trioxide As First-Line Treatment of Acute Promyelocytic Leukemia: A Multicenter Randomized Controlled Trial|
|Zhu, Hong-Hu1; Wu, De-Pei2; Jin, Jie3; Li, Jian-Yong4; Ma, Jun5; Wang, Jian-Xiang6,7,8; Jiang, Hao1; Chen, Sai-Juan9; Huang, Xiao-Jun1|
|刊名||JOURNAL OF CLINICAL ONCOLOGY|
|WOS标题词||Science & Technology|
|关键词[WOS]||TRANS-RETINOIC ACID ; RISK-ADAPTED TREATMENT ; CLINICAL-EFFICACY ; THERAPY ; CELLS ; PHARMACOKINETICS ; ANTHRACYCLINE ; COMBINATION ; MECHANISMS ; MANAGEMENT|
Purpose 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).
Patients and 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.
Conclusion 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.
|项目编号||2006AA02A405 ; 2012AA02A505 ; 2008ZX09312-026 ; Z111107067311070|
|资助机构||National High-Tech RD (863) Program ; Mega Project of the Ministry of Science and Technology ; Beijing Municipal Science & ; Technology Commission|
|作者单位||1.Peking Univ, Peoples Hosp, Beijing 100871, Peoples R China|
2.Harbin Inst Hematol & Oncol, Harbin, Peoples R China
3.Soochow Univ, Affiliated Hosp 1, Suzhou, Jiangsu, Peoples R China
4.Zhejiang Univ, Affiliated Hosp 1, Hangzhou 310003, Zhejiang, Peoples R China
5.Nanjing Med Univ, Affiliated Hosp 1, Jiangsu Prov Hosp, Nanjing, Jiangsu, Peoples R China
6.Chinese Acad Med Sci, Inst Hematol, Tianjin, Peoples R China
7.Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China
8.Peking Union Med Coll, Tianjin, Peoples R China
9.Shanghai Jiao Tong Univ, Rui Jin Hosp, Sch Med, Shanghai 200030, Peoples R China
|Zhu, Hong-Hu,Wu, De-Pei,Jin, Jie,et al. Oral Tetra-Arsenic Tetra-Sulfide Formula Versus Intravenous Arsenic Trioxide As First-Line Treatment of Acute Promyelocytic Leukemia: A Multicenter Randomized Controlled Trial[J]. JOURNAL OF CLINICAL ONCOLOGY,2013,31(33):4215-+.|
|APA||Zhu, Hong-Hu.,Wu, De-Pei.,Jin, Jie.,Li, Jian-Yong.,Ma, Jun.,...&Huang, Xiao-Jun.(2013).Oral Tetra-Arsenic Tetra-Sulfide Formula Versus Intravenous Arsenic Trioxide As First-Line Treatment of Acute Promyelocytic Leukemia: A Multicenter Randomized Controlled Trial.JOURNAL OF CLINICAL ONCOLOGY,31(33),4215-+.|
|MLA||Zhu, Hong-Hu,et al."Oral Tetra-Arsenic Tetra-Sulfide Formula Versus Intravenous Arsenic Trioxide As First-Line Treatment of Acute Promyelocytic Leukemia: A Multicenter Randomized Controlled Trial".JOURNAL OF CLINICAL ONCOLOGY 31.33(2013):4215-+.|