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