Table 2.
Effects of inhaled Azacitidine on 2A: toxicity, response, pulmonary function (FEV1 and DLCO) and 2B: pharmacokinetics (PK, plasma Azacitidine levels).
| 2A. | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Pt | Dose Level mg/m2 |
Cycles (n) |
TRAE | DLT | Response | FEV1 L (% predicted) |
DLCO mL/min/mmHg (% predicted) |
||
| Baseline | End of study |
Baseline | End of study |
||||||
| #1 | 15 | 2 | G1 FEV1 decreased | No | PD | 1.8 (76) | 1.5 (62) | 14.9 (69) | 14.8 (68) |
| #2 | 15 | 2 | None | No | PD | 2.1(109) | 2.2(116) | 13.2 (55) | 15.1 (64) |
| #3 | 15 | 2 | None | No | PD | 1.1 (64) | 1.0 (61) | 6.5 (40) | 6.8 (42) |
| #4 | 30 | 12 | None | No | PR | 2.2 (72) | 2.1 (72) | 17.2 (57) | 22.3 (78) |
| #5 | 30 | 1 | None | No | PD | 1.8 (85) | 1.7 (81) | 19.9 (67) | 18.6 (62) |
| #6 | 30 | 2 | None | No | PD | 1.4 (87) | 1.3 (78) | 9.2 (45) | 8.3 (41) |
| #7 | 45 | 4 | None | No | Stable | 1.6 (54) | 1.7 (61) | 11.2 (33) | 10.9 (33) |
| #8 | 45 | 2 | G2 DLCO decreased (no symptoms) | Yes | Stable | 1.6 (73) | 1.7 (80) | 16.3 (75) | 12.6 (58) |
| TRAE: Treatment-related adverse events. DLT: Dose-limiting toxicity. Pt: patient. Tx: treatment. PD: Progression of Disease. PR: Partial Response. | |||||||||
| 2B. | ||||||||
|---|---|---|---|---|---|---|---|---|
| PK* | Cycle 1 day 1 |
Cycle 1 day 15 | Cycle 1 day 19 | |||||
| Pre- dose |
Pre- dose |
0 h post dose |
2 h post dose |
4h post dose |
Pre- dose |
0 h post dose |
2 h post dose |
|
| Mean plasma (ng/ml) | 0 | 0 | 6.66 | 0.76 | 0 | 0 | 17.87 | 2.48 |
| SEM | 0 | 0 | 9.72 | 0.88 | 0 | 0 | 18.10 | 3.50 |
*
PK summary for 5 patients who received inhaled Azacitidine at 30 and 45mg/m2. (Plasma Azacitidine was undetectable in any of the 3 patients who were treated at the lowest dose level of 15mg/m2).