Table 2.
Clinical Response and Adverse Event Incidence Stratified by Quartiles of Flavopiridol Unbound AUC
| AUC Quartiles | ||||||
|---|---|---|---|---|---|---|
|
| ||||||
| Variable | Category/Units | 1 | 2 | 3 | 4 | p-value |
| n | 29 | 29 | 28 | 29 | ||
|
| ||||||
| Unbound AUC (median [range]) | h* ng/mL | 683 [444, 806] | 946 [808, 1061] | 1252 [1078, 1437] | 1961 [1456, 8234] | <0.001 |
|
| ||||||
| Response (%) | Non-responder | 15 (51.7) | 14 (48.3) | 7 (25.0) | 8 (27.6) | 0.077 |
| Responder | 14 (48.3) | 15 (51.7) | 21 (75.0) | 21 (72.4) | ||
|
| ||||||
| Disease History (%) | Newly diagnosed | 18 (62.1) | 18 (62.1) | 22 (78.6) | 13 (44.8) | 0.077 |
| Relapse-refractory | 11 (37.9) | 11 (37.9) | 6 (21.4) | 16 (55.2) | ||
|
| ||||||
| Dosing Scheme (%) | Bolus | 18 (62.1) | 15 (51.7) | 13 (46.4) | 4 (13.8) | 0.001 |
| Hybrid | 11 (37.9) | 14 (48.3) | 15 (53.6) | 25 (86.2) | ||
|
| ||||||
| Dose Level (%) | 20/30* | 3 (10.3) | 2 (6.9) | 0 (0.0) | 0 (0.0) | NA |
| 25/35* | 2 (6.9) | 3 (10.3) | 1 (3.6) | 0 (0.0) | ||
| 30/40* | 5 (17.2) | 3 (10.3) | 10 (35.7) | 9 (31.0) | ||
| 30/50* | 0 (0.0) | 3 (10.3) | 1 (3.6) | 0 (0.0) | ||
| 30/60* | 1 (3.4) | 3 (10.3) | 3 (10.7) | 15 (51.7) | ||
| 30/70* | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (3.4) | ||
| 50** | 18 (62.1) | 15 (51.7) | 13 (46.4) | 4 (13.8) | ||
|
| ||||||
| Daily Dose (mean (sd)) | mg/m2 | 55.5 (10.2) | 60.3 (14.5) | 62.9 (13.8) | 78.6 (15.1) | <0.001 |
|
| ||||||
| ALT (%) | 0 | 26 (89.7) | 29 (100) | 27 (96.4) | 28 (96.6) | 0.335 |
| 1 | 3 (10.3) | 0 (0.0) | 1 (3.6) | 1 (3.4) | ||
|
| ||||||
| AST (%) | 0 | 26 (89.7) | 27 (93.1) | 26 (92.9) | 26 (89.7) | 1 |
| 1 | 3 (10.3) | 2 (6.9) | 2 (7.1) | 3 (10.3) | ||
|
| ||||||
| BILI (%) | 0 | 27 (93.1) | 28 (96.6) | 27 (96.4) | 26 (89.7) | 0.834 |
| 1 | 2 (6.9) | 1 (3.4) | 1 (3.6) | 3 (10.3) | ||
|
| ||||||
| Cardiac (%) | 0 | 28 (96.6) | 29 (100) | 28 (100) | 29 (100) | 1 |
| 1 | 1 (3.4) | 0 (0.0) | 0 (0.0) | 0 (0.0) | ||
|
| ||||||
| Creatinine (%) | 0 | 29 (100) | 29 (100) | 28 (100) | 29 (100) | NA |
| 1 | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | ||
|
| ||||||
| Diarrhea (%) | 0 | 29 (100) | 27 (93.1) | 28 (100) | 28 (96.6) | 0.615 |
| 1 | 0 (0.0) | 2 (6.9) | 0 (0.0) | 1 (3.4) | ||
|
| ||||||
| Mucositis (%) | 0 | 28 (96.6) | 28 (96.6) | 28 (100) | 27 (93.1) | 0.901 |
| 1 | 1 (3.4) | 1 (3.4) | 0 (0.0) | 2 (6.9) | ||
|
| ||||||
| Nausea (%) | 0 | 27 (93.1) | 29 (100) | 26 (92.9) | 28 (96.6) | 0.569 |
| 1 | 2 (6.9) | 0 (0.0) | 2 (7.1) | 1 (3.4) | ||
|
| ||||||
| Rash (%) | 0 | 29 (100) | 29 (100) | 28 (100) | 29 (100) | NA |
| 1 | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | ||
|
| ||||||
| TLS (%) | 0 | 28 (96.6) | 26 (89.7) | 28 (100) | 27 (93.1) | 0.509 |
| 1 | 1 (3.4) | 3 (10.3) | 0 (0.0) | 2 (6.9) | ||
|
| ||||||
| Vomiting (%) | 0 | 28 (96.6) | 29 (100) | 26 (92.9) | 29 (100) | 0.191 |
| 1 | 1 (3.4) | 0 (0.0) | 2 (7.1) | 0 (0.0) | ||
|
| ||||||
| Unbound Cmax (median [range]) | ng/mL | 80.9 [31.6, 111] | 86.4 [39.3, 147] | 89.0 [51.3, 152] | 120 [69.8, 375] | <0.001 |
*
bolus:infusion in mg/m2/day units;
**
in units of mg/m2/day; for binary variables, presence or absence are denoted by 1 or 0, respectively;
’newdiag’ = newly diagnosed patient; ‘rel-refr’ = relapsed/refractory patient