The comparison of plasma arsenic concentration and urinary arsenic excretion during treatment with Realgar-Indigo naturalis formula and arsenic trioxide in children with acute promyelocytic leukemia

doi:10.1007/s00280-022-04449-9

Clinical Trial

. 2022 Jul;90(1):45-52.

doi: 10.1007/s00280-022-04449-9. Epub 2022 Jun 27.

The comparison of plasma arsenic concentration and urinary arsenic excretion during treatment with Realgar-Indigo naturalis formula and arsenic trioxide in children with acute promyelocytic leukemia

Liu-Hua Liao^#^{1

2}, Yi-Qiao Chen^#³, Dan-Ping Huang^#¹, Li-Na Wang⁴, Zhong-Lu Ye⁵, Li-Hua Yang⁶, Hui-Rong Mai⁷, Yu Li¹, Cong Liang¹, Jie-Si Luo¹, Li-Na Wang¹, Xue-Qun Luo¹, Yan-Lai Tang⁸, Xiao-Li Zhang⁹, Li-Bin Huang¹⁰

Affiliations

¹ Department of Pediatrics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
² Department of Pediatrics, Huizhou Municipal Central Hospital, Huizhou, China.
³ Department of Pediatric Hematology, Fujian Medical University Union Hospital, Fuzhou, China.
⁴ Department of Pediatrics, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, China.
⁵ Department of Children's Medical Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
⁶ Pediatric Center of Zhujiang Hospital, Southern Medical University, Guangzhou, China.
⁷ Department of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen, China.
⁸ Department of Pediatrics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. tangylai@mail.sysu.edu.cn.
⁹ Department of Pediatrics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. sealuda@sina.com.
¹⁰ Department of Pediatrics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. huanglb3@mail.sysu.edu.cn.

^# Contributed equally.

PMID: 35760920
DOI: 10.1007/s00280-022-04449-9

Clinical Trial

The comparison of plasma arsenic concentration and urinary arsenic excretion during treatment with Realgar-Indigo naturalis formula and arsenic trioxide in children with acute promyelocytic leukemia

Liu-Hua Liao et al. Cancer Chemother Pharmacol. 2022 Jul.

. 2022 Jul;90(1):45-52.

doi: 10.1007/s00280-022-04449-9. Epub 2022 Jun 27.

Authors

Affiliations

¹ Department of Pediatrics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
² Department of Pediatrics, Huizhou Municipal Central Hospital, Huizhou, China.
³ Department of Pediatric Hematology, Fujian Medical University Union Hospital, Fuzhou, China.
⁴ Department of Pediatrics, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, China.
⁵ Department of Children's Medical Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
⁶ Pediatric Center of Zhujiang Hospital, Southern Medical University, Guangzhou, China.
⁷ Department of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen, China.
⁸ Department of Pediatrics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. tangylai@mail.sysu.edu.cn.
⁹ Department of Pediatrics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. sealuda@sina.com.
¹⁰ Department of Pediatrics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. huanglb3@mail.sysu.edu.cn.

^# Contributed equally.

PMID: 35760920
DOI: 10.1007/s00280-022-04449-9

Abstract

Realgar-Indigo naturalis formula (RIF) is a traditional Chinese medicine containing As₄S₄ and effective in treating acute promyelocytic leukemia (APL). The dose of RIF remains to be determined in pediatric patients. Comparison of plasma arsenic concentrations and toxicity between RIF and arsenic trioxide (ATO) treatment in APL may help to establish an appropriate therapeutic dose of RIF for children. From October 2018 to March 2020, 19 pediatric patients with APL treated with SCCLG-APL protocol were included, 9 in RIF group at 135 mg/kg/day orally three times daily, and 10 in ATO group at 0.16 mg/kg/day intravenously over 12 h daily. Peak and trough plasma arsenic concentrations were assayed at D1, 2, 7 and 14 of induction treatment. Urine arsenic excretions were assessed with spot urine samples and the measurements were adjusted using creatinine. Toxicities were compared between two groups. The plasma arsenic concentration reached steady state at D7 either in the RIF or ATO group, and the mean peak and trough concentrations were similar between two groups (P > 0.05), which were 0.54 μmol/L and 0.48 μmol/L in RIF group, and 0.63 μmol/L and 0.51 μmol/L in ATO group, respectively. Urine arsenic excretion rate was positively correlated with the concentration of plasma arsenic. The rates of treatment-related adverse events were similar in two groups. In conclusion, the dose of RIF at 135 mg/kg/day may be an appropriate therapeutic dose in children with APL. Urine arsenic level can be used as an indicator to estimate plasma arsenic concentration. Trial registration www.clinicaltrials.gov NCT02200978.

Keywords: Acute promyelocytic leukemia; Arsenic concentration; Children; Urine arsenic excration rate.

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References

1. Yang MH, Wan WQ, Luo JS et al (2018) Multicenter randomized trial of arsenic trioxide and Realgar-Indigo naturalis formula in pediatric patients with acute promyelocytic leukemia: Interim results of the SCCLG-APL clinical study. Am J Hematol 93(12):1467–1473. https://doi.org/10.1002/ajh.25271 - DOI - PubMed - PMC
1. Zhu HH, Wu DP, Jin J et al (2013) Oral tetra-arsenic tetra-sulfide formula versus intravenous arsenic trioxide as first-line treatment of acute promyelocytic leukemia: a multicenter randomized controlled trial. J Clin Oncol 31:4215–4221. https://doi.org/10.1200/JCO.2013.48.8312 - DOI - PubMed
1. Wang L, Zhou GB, Liu P et al (2008) Dissection of mechanisms of Chinese medicinal formula Realgar-indigo naturalis as an effective treatment for promyelocytic leukemia. Proc Natl Acad Sci USA 105:4826–4831. https://doi.org/10.1073/pnas.0712365105 - DOI - PubMed - PMC
1. Bi LL, Ma Q, Wang SQ et al (2005) Treatment of 32 cases with recurring acute promyelocytic leukemia with tablets of composite natural indigo. Zhonghua Er Ke Za Zhi Sep 43(9):702–703. https://doi.org/10.3760/j.issn:0578-1310.2005.09.020 - DOI
1. Luo XQ, Ke ZY, Huang LB et al (2009) Improved outcome for Chinese children with acute promyelocytic leukemia: a comparison of two protocols. Pediatr Blood Cancer 53(3):325–328. https://doi.org/10.1002/pbc.22042 - DOI - PubMed

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[1] Yang MH, Wan WQ, Luo JS et al (2018) Multicenter randomized trial of arsenic trioxide and Realgar-Indigo naturalis formula in pediatric patients with acute promyelocytic leukemia: Interim results of the SCCLG-APL clinical study. Am J Hematol 93(12):1467–1473. https://doi.org/10.1002/ajh.25271 - DOI - PubMed - PMC

[2] Yang MH, Wan WQ, Luo JS et al (2018) Multicenter randomized trial of arsenic trioxide and Realgar-Indigo naturalis formula in pediatric patients with acute promyelocytic leukemia: Interim results of the SCCLG-APL clinical study. Am J Hematol 93(12):1467–1473. https://doi.org/10.1002/ajh.25271 - DOI - PubMed - PMC

[3] Zhu HH, Wu DP, Jin J et al (2013) Oral tetra-arsenic tetra-sulfide formula versus intravenous arsenic trioxide as first-line treatment of acute promyelocytic leukemia: a multicenter randomized controlled trial. J Clin Oncol 31:4215–4221. https://doi.org/10.1200/JCO.2013.48.8312 - DOI - PubMed

[4] Zhu HH, Wu DP, Jin J et al (2013) Oral tetra-arsenic tetra-sulfide formula versus intravenous arsenic trioxide as first-line treatment of acute promyelocytic leukemia: a multicenter randomized controlled trial. J Clin Oncol 31:4215–4221. https://doi.org/10.1200/JCO.2013.48.8312 - DOI - PubMed

[5] Wang L, Zhou GB, Liu P et al (2008) Dissection of mechanisms of Chinese medicinal formula Realgar-indigo naturalis as an effective treatment for promyelocytic leukemia. Proc Natl Acad Sci USA 105:4826–4831. https://doi.org/10.1073/pnas.0712365105 - DOI - PubMed - PMC

[6] Wang L, Zhou GB, Liu P et al (2008) Dissection of mechanisms of Chinese medicinal formula Realgar-indigo naturalis as an effective treatment for promyelocytic leukemia. Proc Natl Acad Sci USA 105:4826–4831. https://doi.org/10.1073/pnas.0712365105 - DOI - PubMed - PMC

[7] Bi LL, Ma Q, Wang SQ et al (2005) Treatment of 32 cases with recurring acute promyelocytic leukemia with tablets of composite natural indigo. Zhonghua Er Ke Za Zhi Sep 43(9):702–703. https://doi.org/10.3760/j.issn:0578-1310.2005.09.020 - DOI

[8] Bi LL, Ma Q, Wang SQ et al (2005) Treatment of 32 cases with recurring acute promyelocytic leukemia with tablets of composite natural indigo. Zhonghua Er Ke Za Zhi Sep 43(9):702–703. https://doi.org/10.3760/j.issn:0578-1310.2005.09.020 - DOI

[9] Luo XQ, Ke ZY, Huang LB et al (2009) Improved outcome for Chinese children with acute promyelocytic leukemia: a comparison of two protocols. Pediatr Blood Cancer 53(3):325–328. https://doi.org/10.1002/pbc.22042 - DOI - PubMed

[10] Luo XQ, Ke ZY, Huang LB et al (2009) Improved outcome for Chinese children with acute promyelocytic leukemia: a comparison of two protocols. Pediatr Blood Cancer 53(3):325–328. https://doi.org/10.1002/pbc.22042 - DOI - PubMed

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The comparison of plasma arsenic concentration and urinary arsenic excretion during treatment with Realgar-Indigo naturalis formula and arsenic trioxide in children with acute promyelocytic leukemia

Affiliations

The comparison of plasma arsenic concentration and urinary arsenic excretion during treatment with Realgar-Indigo naturalis formula and arsenic trioxide in children with acute promyelocytic leukemia

Authors

Affiliations

Abstract

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