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Journal of Chinese Integrative Medicine ›› 2009, Vol. 7 ›› Issue (9): 801-808.doi: 10.3736/jcim20090901

• Systematic Review •     Next Articles

Efficacy of arsenic trioxide for acute promyelocytic leukemia: A systematic review and meta-analysis

Shuang-nian Xua,Jie-ping Chena,Jian-ping Liub,Yun Xiab   

  1. a Center for Hematology,Southwest Hospital, Third Military Medical University, Chongqing 400038, China
    b Center for Evidence-Based Medicine,Beijing University of Chinese Medicine, Beijing 100029, China
  • Received:2009-06-04 Accepted:2009-08-04 Online:2009-09-20 Published:2009-09-15
  • Contact: Jie-ping Chen, Jian-ping Liu E-mail:chenjpxn@yahoo.com.cn;jianping_l@hotmail.com

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Objective

To systematically review the efficacy and safety of arsenic trioxide (ATO) in treatment of acute promyelocytic leukemia (APL).
Methods

The Cochrane Library (Issue 1, 2009), Cochrane Central Register of Controlled Trials (from 1970 to January 2009), MEDLINE (from 1978 to October 2008), EMBASE (from 1950 to March 2009), Chinese Biological Medical Literature Database (from 1978 to December 2008), China National Knowledge Infrastructure (CNKI, from 1994 to December 2008), and China Medical Academic Conference Database (from 1994 to December 2008) were electronically searched. We also searched the Meta-Register of controlled trials, Conference Proceedings of American Society of Hematology (from 1946 to December 2008) and Conference Proceedings of American Society of Clinical Oncology (from 1946 to December 2008) on the internet for grey literature. The related journals in the library of Third Military Medical University were hand-searched. The randomized controlled trials (RCTs) of ATO in treatment of APL were included. We adopted complete remission, overall survival rate, disease free survival rate, time to complete remission, relapse rate, mortality and adverse reactions as outcome indicators. Data were entered and analyzed with the Cochrane review manager software 5.0 (RevMan 5.0).
Results

After merger of the included trials, five eligible RCTs with 328 cases were included. All the RCTs focused on the comparison of all-trans retinoic acid (ATRA) plus ATO regimen with ATRA monotherapy. Meta-analysis showed that the effect indexes for time to complete remission, two-year disease free survival rate, relapse rate, incidence of edema and incidence rate of QT interval prolongation were –1.20 [–1.68, –0.72], 8.64 [1.66,45.00], 0.21 [0.09,0.47], 4.16 [1.46,11.79] and 22.10 [2.75,177.49], respectively. The influences on other outcome indicators such as complete remission and leukocytosis were statistically non-significant.
Conclusion

ATO can prolong disease free survival and reduce the time to complete remission and relapse rate of newly diagnosed APL patients, and increase the incidence of edema and prolongation of corrected QT interval during the treatment. Due to limitation of the included trials, this conclusion needs to be validated by further studies.

Key words: Arsenic trioxide, Leukemia, Promyelocytic, Acute, Randomized controlled trial, Systematic review, Meta-analysis

Figure 1

Flow diagram of literature searching and screening"

Table 1

Basic characteristics of the included studies"

Study Cases* Male/Female△ Median age (years)▲ White blood cell count ($\bar{x}$±s, 109/L) Treatment program
ATO (–) group ATO (+) group ATO (–) group ATO (+) group ATO (–) group ATO (+) group ATO (–) group ATO (+) group ATO (–) group ATO (+) group
Shen et al[14] 20 21 12/8 9/12 30.5 34 Did not report Did not report ATRA 25 mg/(m2·d) ATO 0.16 mg/(kg·d); ATRA 25 mg/(m2·d)
Su et al [15] 30 40 12/18 18/22 31 37.2 11.9±21.5 15.7±20.6 ATRA 25 mg/(m2·d) ATO 0.16 mg/(kg·d); ATRA 30-40 mg/d
Ren et al [16] 52 43 30/22 23/20 32 34 11.9±21.5 13.6±23.9 ATRA 25 mg/(m2·d) ATO 10 mg/d; ATRA 25 mg/(m2·d)
Yang et al[17] 11 15 4/7 5/10 41 39 Did not report Did not report ATRA 30-60 mg/d ATO 10 mg/d; ATRA 30-60 mg/d
Zhou et al [9,10,11,12,13] 48 48 30/18 28/20 23 21 7.8±3.0 8.2±2.5 ATO 0.16 mg/(kg·d), routine intravenous infusion (30-40 drops per minute) ATO 0.16 mg/(kg·d), continuous slow intravenous infusion (8 drops per minute)

Figure 2

Bias risk from the included trials"

Figure 3

Summary of the bias risk from the included trials"

Figure 4

Effects of adding ATO on complete remission rate of APL patients"

Figure 5

Effects of adding ATO on the relapse rate of APL patients"

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