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Table 6 Correlation of clinical responses and plasma concentrations of 5-AZA-CdR in patients with hematological malignancies

From: Pharmacokinetic and pharmacodynamic analysis of 5-aza-2’-deoxycytidine (decitabine) in the design of its dose-schedule for cancer therapy

Type of leukemia

Dose-schedule

Duration infusion

Estimated plasma concentration

Estimated AUC (μM × hour)

Response %ORR (%CR)

References

AMLa

ind: 135 mg/m2main:20 mg/m2

1 to 72 hours

0.12 to 1.25 μM

0.12 to 90

26

[143]

AML

20 mg/m2

1 hour

1.25 μM

1.25

25 (24)

[110]

AML

20 mg/m2

1 hour

1.25 μM

1.25

64 (47)

[144]

CMML

15 mg/m2

3 to 4 hours

0.24 to 0.31 μM

0.72 to 1.24

25(11)

[105, 145, 146]

AML

20 mg/m2

1 hour

1.25 μM

1.25

67 (26)

[147]

CML

50 to 100 mg/m2

6 hour

0.52 to 1.0 μM

3.12 to 6.0

B28(10),A55(23),C63(13)

[148]

CML

50 to 100 mg/m2

6 hours

0.52 to 1.0 μM

3.12 to 6.0

53 (0)

[121, 122]

CML

50 to 100 mg/m2

6 hours

0,52 to 1,0 μM

3.12 to 6.0

84 (10)

[121, 122]

AMLb

90 mg/m2

4 hours

1.41 μM

5.64

100 (100)

[149]

AMLc

125 to 250 mg/m2

6 hours

1.3 to 2.6 μM

7.8 to 15.6

44 (44)

[150]

AMLd

125 to 250 mg/m2

6 hours

1.3 to 2.6 μM

7.8 to 15.6

41 (41)

[151]

AMLd

125 to 250 mg/m2

6 hours

1.3 to 2.6 μM

7.8 to 15.6

82(73)

[137]

AML

250 to 500 mg/m2

6 hours

2.61 to 5.2 μM

15.66 to 31.2

20 (0)

[137]

AML

270 to 360 mg/ m2/day t.i.d.

4 hours

4.2 to 5.6 μM

16.8 to 22.4

40 (30)

[109]

AML, ALL, CML

300 to 500 mg/m2/day c. i.v.

24 to 120 hours

0.16 to 1.3 μM

3.84 to 156.0

26 (4)

[108]

AML, ALL

37 to 80 mg/kg c.i.v.

36 to 60 hours

1.4 to 5.15 μM

50.4 to 309.0

37 (22)

[97]

AML, ALL

0.75 to 80 mg/kg conti.i.v.

12 to 44 hours

0.04 to 15 μM

9.0 to 660.0

14 (9)

[7]

  1. ain combination with ATRA; bin combination with daunorubicin; cin combination with idarubicin; din combination with amsacrine. 1 μM= 228 ng/ml. 5-AZA-CdR, 5-aza-2′-deoxycytidine; A, accelerated; ALL, acute lymphocytic leukemia; AML, acute myeloid leukemia; ATRA, all trans retinoic acid; AUC, area under the curve; B, blastic; C, chronic; CML, chronic myeloid leukemia; CMML, chronic myelomonocytic leukemia; CR, complete remission; ORR, overall response rate.