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. Author manuscript; available in PMC: 2016 May 27.
Published in final edited form as: Clin Cancer Res. 2014 Oct 1;20(19):4985–4993. doi: 10.1158/1078-0432.CCR-13-2725

Table 1. A summary of prospective trials that used arsenic along with other agents (not as single agent) in the upfront management of patients with newly diagnosed APL.

Risk groupa (# patients)
Study, type of study, # of patients (ref.) Follow-up, median (range) in months Age, median (range) in years High Non-high Induction (CR%) Consolidation Maintenance Survival
Induction consolidation maintenance in combination with other agents
Shen et al., randomized, 61, (46) 18 (8–30) 30.5–39.5 (14–74) 14 47 Randomized to:

  • ATRA (95%)

  • ATO (90%)

  • ATRA+ATO (95.2%)

 Three courses of sequential DA-cytarabine “pulse” regimen-HA Five cycles of either:

  • ATRA+6-MP+MTX

  • ATO+6-MP+MTX

  • ATRA+ATO+6-MP+MTX

 Median DFS (mo):

  • ATRA: 13

  • ATO: 16

  • ATRA+ATO: 20
Estey et al., single-arm, 44, (47) 16 (N/A) 45 19 25 ATRA+ATO (+GO for high-risk; 89%) Four courses of ATRA–ATO (28 weeks) No additional therapy 2-year OS: 86%
2-year DFS: 86%
Ravandi et al., single-arm, 82, (48) 23 (0.47–65.6) 47 (14–81) 26 56 ATRA+ATO (+GO for high-risk; 92%) Four courses of ATRA–ATO (28 weeks) No additional therapy 3-year OS: 85%
3-year DFS: 81 %
Hu et al., single-arm, 85, (38) 70 (21–88) N/A(<15–>55) 19 66 ATRA+ATO (+hydroxyurea for high-risk; 94.1%) Three courses of sequential DA-cytarabine “pulse” regimen-HA Five cycles of either:

  • ATRA+6-MP+MTX

  • ATO+6-MP+MTX

  • ATRA+ATO+6-MP+MTX

 5-year OS: 91.7%
5-year EFS: 89.2%
5-year DFS: 94.8%
Dai et al., nonrandomized, two-arm, 162, (69) 30–32 (1–59) 32–34 (14–69) 39 123 Group A (72 patients): ATRA (90.3%)
Group B (90 patients): ATRA+ATO (93.3%, P = 0.57)		 Group A: A2: Five cycles of ATRA+DA+HA;
A1: Four cycles of ATRA+DA+ HA+ one cycle of ATO
Group B: Four cycles of ATRA+DA+HA+ one cycle of ATO		 Group A: A2: 2 years of ATRA+DA+HA;
A1: 2 years of ATRA+ATO+DA
Group B: 2 years of ATRA+ATO+DA		 3-year DFS:

  • Group A2 (no ATO): 72.4%

  • Group A1 (ATO in consolidation and maintenance): 93.8%

  • Group B (ATO in induction, consolidation, and maintenance): 92.6%
Iland et al., single-arm, 124, (51) 24 (2–61) 44 (3–78) 24 99 ATRA+ ATO+lda (95%) Two courses of ATO+ATRA 2 years (eight cycles) of ATRA, 6-MP, and MTX 2-year OS: 93.2%
2-year EFS: 88.1%
2-year DFS: 98%
Lo-Coco et al., randomized noninferiority, 156, (43) 34.4 (0.5–55.8) 44.6–46.6 (18.7–70.2) 0 156 Randomized (1:1) to:

  • ATRA–ATO(100%)

  • ATRA-lda (95%, P=0.12)

 For ATRA–ATO group: four courses of ATRA–ATO (28 weeks)
For ATRA-lda group: three sequential cycles of ATRA-lda, ATRA-Mitroxantrone, ATRA-lda.		 For ATRA-ATO: No additional therapy
For ATRA-lda group: 2 years of ATRA, 6-MP, and MTX		 2-year EFS:

  • ATRA-ATO: 97%

  • ATRA-lda: 86% (noninferiority P < 0.001, superiority P = 0.02).

2-year OS:

  • ATRA–ATO:99%

  • ATRA-lda: 91 % (P = 0.02)
Zhu et al., randomized noninferiority, 242, (56) 39 (21–64) 36 (15–60) 46 185 Randomized (1:1) to: Oral RIF (an AS4S4-containing formula) + ATRA(99.1%) ntravenous ATO+ATRA (97.4%, P = 0.62) Both groups received three sequential cycles of HA, MA, and DA. For RIF+ATRA group: 2 years of RIF-ATRA
For ATO+ATRA group: 2 years of ATO-ATRA		 2-year DFS:

  • ATRA+AS4S4: 98.1 %

  • ATRA+ATO: 95.5% (noninferiority P< 0.001) 3-year OS:

  • ATRA+As4S4: 99.1%

  • ATRA+ATO: 96.6% (P = 0.18)
Consolidation
Gore et al., single-arm, 45, (49) 32.4 (18–66) 50 (19–70) 14 31 ATRA+daunorubicin One course of cytarabine + daunorubicin+ATO High-risk: 2 years of ATRA, 6-MP, and MTX Low-risk: 2-year (ATRA) 3-year OS: 88%
3-year DFS: 88.7%
3-year EFS: 76%
Powell et al., randomized, 481, (21) 28.8 (N/A) N/A (15–79) 113 368 ATRA+ cytarabine+ D aunorubicin (90%) Randomized (1:1) to: 2 courses of ATRA+daunorubicin Two courses of ATO followed by two courses of ATRA+ Daunorubicin Randomized to one year of:

  • ATRA

  • ATRA+6-MP+MTX

 3-year EFS:

  • ATO arm: 80%

  • Non-ATO arm: 63% (P< 0.0001)

3-year OS:

  • ATO arm: 86%

  • Non-ATO arm: 81% (P= 0.059)

3-year DFS:

  • ATO arm: 90%

  • Non-ATO arm: 70% (P < 0.0001)
Maintenance therapy
Au et al., single-arm, 76, (54) 24 (1–115) 44 (16–83) 10 66 For patients <65 years old: ATRA+ 7 and three regimen (daunorubicin and cytarabine)b
For older patients: ATRA-ATOb 		For patients <65 years old: two cycles of daunorubicin and cytarabineb
For older patients: no consolidation, went directly to maintenanceb 		One of 3 regimens (evolved over course of study):

  • Oral ATO

  • Oral ATO+ATRA

  • Oral ATO+ATRA+ ascorbic acid

 3-year OS: 90.6%
3-year DFS: 87.7%
3-year EFS: 83.7%
(type of maintenance did not affect survival rates)

Abbreviations: DA, daunorubicin + cytarabine; HA, homoharringtonine + cytarabine; Ida, Idarubicin; N/A, not available; MA, mitoxantrone + cytarabine; RIF, Realgar-Indigo naturalis (an AS4S4-containing formulation).

a

Risk grouping according to Sanz et al. (70).

b

All patients were required to be in CR after induction and consolidation at registration for the trial.