Table 2.
Anagrelide dosing and modification: safety set
| ANA therapy | Subgroup totals | Total (n = 175) | ||||||
|---|---|---|---|---|---|---|---|---|
| Discontinuation of previous CRT2 | CRT discontinued after ANA | Dosing with SPC recommendations2 | ||||||
| Before ANA (n = 115) | After ANA (n = 39) | Not discontinued (n = 16) | 0–1 month (n = 30) | 1–6 months (n = 9) | Consistent (n = 133) | Inconsistent (n = 37) | ||
| Starting daily dose (mg/d) Median (range) | 1.0 (0.3–1.5) | 0.5 (0.5–1.3) | 1.0 (0.5–1.0) | 0.5 (0.5–1.3) | 0.5 (0.5–1.0) | 1.0 (0.5–1.0) | 1.0 (0.3–1.5) | 1.0 (0.3–1.5) |
| Maximum daily dose (mg/d) Median (range) | 1.5 (0.5–4.0) | 1.5 (0.5–3.0) | 1.3 (1.0–2.5) | 1.5 (0.5–3.0) | 2.0 (1.0–3.0) | 1.5 (0.5–4.0) | 2.0 (1.0–3.5) | 1.5 (0.5–4.0) |
| Last daily dose (mg/d) Median (range) | 1.5 (0.3–4.0) | 1.5 (0.5–3.0) | 1.0 (1.0–2.0) | 1.4 (0.5–3.0) | 1.5 (0.8–3.0) | 1.0 (0.3–4.0) | 2.0 (0.5–3.5) | 1.5 (0.3–4.0) |
| Dose modifications, n (%) | ||||||||
| Total dose increases | 83 (72.2) | 35 (89.7) | 13 (81.3) | 27 (90.0) | 8 (88.9) | 98 (73.7) | 33 (89.2) | 135 (77.1) |
| Reasons | ||||||||
| ≥1 platelet objective not reached | 64 (77.1) | 24 (68.6) | 8 (61.5) | 19 (70.4) | 5 (62.5) | 71 (72.4) | 25 (75.8) | 99 (73.3)3 |
| ≥1 preplanned dose titration | 30 (36.1) | 21 (41.4) | 6 (41.2) | 17 (63.0) | 4 (50.0) | 43 (43.9) | 14 (42.4) | 58 (43.0)3 |
| Total dose decreases | 24 (20.9) | 19 (48.7) | 5 (31.3) | 15 (50.0) | 4 (44.4) | 35 (26.3) | 13 (35.1) | 50 (28.6) |
| Reasons | ||||||||
| ≥1 ADR | 10 (41.7) | 6 (31.6) | 4 (80.0) | 6 (40.0) | 0 | 13 (37.1) | 7 (53.8) | 21 (42.0)3 |
| ≥1 other reason | 9 (37.5) | 8 (42.1) | 0 | 6 (40.0) | 2 (50.0) | 13 (37.1) | 4 (30.8) | 18 (36.0)3 |
| ≥1 platelet objective not reached | 4 (16.7) | 2 (10.5) | 1 (20.0) | 1 (6.7) | 1 (25.0) | 4 (11.4) | 3 (20.1) | 7 (14.0)3 |
| ≥1 preplanned dose titration | 5 (20.8) | 3 (15.8) | 0 | 2 (13.3) | 1 (25.0) | 6 (17.1) | 2 (15.4) | 8 (16.0)3 |
| Total dose interruptions | 10 (8.7) | 5 (12.8) | 1 (6.3) | 3 (10.0) | 2 (22.2) | 11 (8.3) | 5 (13.5) | 16 (9.1) |
| Reasons | ||||||||
| ≥1 ADR | 6 (60.0) | 3 (60.0) | 0 | 2 (66.7) | 1 (50.0) | 6 (54.5) | 3 (60.0) | 9 (56.3)3 |
| ≥1 other reason | 4 (40.0) | 2 (40.0) | 1 (100.0) | 1 (33.3) | 1 (50.0) | 5 (45.5) | 2 (40.0) | 7 (43.8)3 |
| Total anagrelide discontinuations | 20 (17.4) | 5 (12.8) | 3 (18.8) | 4 (13.3) | 1 (11.1) | 24 (18.0) | 4 (10.8) | 30 (17.1) |
| Reasons | ||||||||
| ADR | 16 (80.0) | 4 (80.0) | 2 (66.7) | 4 (100.0) | 0 | 19 (79.2) | 3 (75.0) | 24 (80.0)3 |
| Death | 2 (10.0) | 1 (20.0) | 0 | 0 | 1 (100.0) | 2 (8.3) | 1 (25.0) | 3 (10.0)3 |
| Disease progression | 1 (5.0) | 0 | 0 | 0 | 0 | 1 (4.2) | 0 | 1 (3.3)3 |
| Intercurrent disease | 1 (5.0) | 0 | 0 | 0 | 0 | 1 (4.2) | 0 | 1 (3.3)3 |
| Lack of efficacy | 0 | 0 | 1 (33.3) | 0 | 0 | 1 (4.2) | 0 | 1 (3.3)3 |
| No modification since starting dose | 21 (18.3) | 2 (5.1) | 3 (18.8) | 2 (6.7) | 0 | 22 (16.5) | 4 (10.8) | 26 (14.9) |
ADR, adverse drug reaction; ANA, anagrelide; CRT, cytoreductive therapy; SPC, Summary of Product Characteristics.
Data not shown for five additional patients included in the study who had no prior cytoreductive therapy and therefore received anagrelide as a first-line treatment.
Percentage calculated from the total of each dose modification.