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Oral tetra-arsenic tetra-sulphide formula achieved similar efficacy and safety compared to intravenous arsenic trioxide as first-line treatment of APL.

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Presentation on theme: "Oral tetra-arsenic tetra-sulphide formula achieved similar efficacy and safety compared to intravenous arsenic trioxide as first-line treatment of APL."— Presentation transcript:

1 Oral tetra-arsenic tetra-sulphide formula achieved similar efficacy and safety compared to intravenous arsenic trioxide as first-line treatment of APL (multi-center randomized controlled trial APL07) Hong-Hu Zhu, De-Pei Wu, Jie Jin, Jian-Yong Li, Jun Ma, Jian-Xiang Wang, Hao Jiang, Gordon G. Liu, Sai-Juan Chen, Xiao-Jun Huang Peking University Institute of Hematology ( PUIH ) Peking University People’s Hospital, Beijing, P.R.C.

2 Arsenic plays a key role in cure of APL Introduction Chen SJ, et al. Blood 2011;117:6425 Shen ZX, et al. PNAS 2004;101:5328 Hu J, et al. PNAS 2009;106:3342 Sanz MA, et al. Blood 2010;115:5137 (ATO: arsenic trioxide)

3 Intravenous vs. Oral arsenic Effective inconvenient : iv Inpatients Introduction Lu DP, et al. Blood 2002; 99:3136 Xiang Y, et al. Chin J Clin Hematol 2007;16:204 Wang L, et al. PNAS 2008;105:4826 Intravenous arsenicOral arsenic Effective convenient : oral Outpatients

4 Question No randomised controlled trial to answer whether oral arsenic has similar efficacy and safety with intravenous arsenic in treating APL. Introduction

5 Purpose of our study To demonstrate oral arsenic can be used in place of arsenic trioxide as first-line treatment in newly diagnosed APL Multicenter, randomised controlled trial Introduction

6 Design Chinese APL Cooperative Group(7 Centers) Multicenter, randomised controlled trial: APL07 (registered number ChiCTR -TRC ) Enrollment : to Last follow-up: (median 32 months) Methods

7 Arsenic used in our study Control group: intravenous arsenic trioxide(As2O3, ATO) Trial group: oral tetra-arsenic tetra-sulphide formula (As4S4; Realgar-Indigo naturalis formula, RIF ) Lu DP, et al. Blood 2002; 99:3136 Xiang Y, et al. Chin J Clin Hematol 2007;16:204 Wang L, et al. PNAS 2008;105:4826 Methods

8 Inclusion Criteria de novo APL Age :15-60 years WBC <50×10 9 /L before treatment Adequate hepatic and renal function Performance Status score 0-2 Able to provide written informed consent Methods

9 Trial Design HA: homoharringtonine ; cytarabine MA: mitoxantrone ; cytarabine DA: daunorubicin ; cytarabine RIF: Realgar-Indigo naturalis formula ATO: Arsenic trioixide ATRA: all-trans retinoic acid Methods

10 Induction Therapy RIF: 60 mg/kg, d1-CR ATO : 0.16 mg per kg, d1-CR ATRA: 25 mg/m2, d1-CR Mitoxantrone 1.4 mg/m2, for 5-10 days Methods

11 Consolidation Therapy HA homoharringtonine 2 mg/m2 for 7 days cytarabine 100 mg/m2 for 5 days MA mitoxantrone 6 mg/m2 for 3 days cytarabine 100 mg/m2 for 5 days DA daunorubicin 40 mg/m2 for 3 days cytarabine 100 mg/m2 for 5 days Methods

12 Maintenance Therapy RIF: 60 mg/kg, for14 days ATO : 0.16 mg per kg, for14 days ATRA: 25 mg/m2, for14 days Methods

13 Endpoints Primary endpoint: `Disease-Free Survival (DFS) Second endpoints: Complete remission (CR) Overall survival (OS) Safety Methods

14 Trial Profile of APL07 Methods

15 Patients Characteristics RIF group ATO group Characteristic (n=114) (n=117) p Age (yr) 33(15-60)39(15-60) ns Median (range) Sex ( M/F) 61/5365/52 ns WBC (10 9 /L) 2.1( )2.2( ) ns Median (range) PLT(10 9 /L) 29(5-333)31(5-164) ns Median (range) Sanz Score ns Low-risk3339 Intermediate-risk6053 High-risk2125 Blasts (BM)(%) 82(35-96) 81(19-96) ns Results

16 Outcome of RIF and ATO RIF group ATO group (n=114) (n=117) Outcome No.% % P CR Induction failure Dead13 no CR00 DFS Living in CR112 Death during CR01 Relapse11 OS Living113 Dead 1 4 Results

17 Disease-Free Survival 99.0% ( 3ys) 98.2% (3ys) Results

18 Overall Survival 99.1% ( 3ys) 96.6% ( 3ys) Results

19 Molecular Kinetics RIFATO Results

20 Similar liver toxicity Results RIFATORIFATO Induction Maintenance

21 Similar differentiation syndrome RIFATO 19% 25%

22 Conclusions Oral arsenic achieves similar efficacy and safety when compared to intravenous arsenic trioxide Our results suggest that arsenic/ATRA/ chemo combination might be an alternative to current frontline treatment of APL

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