Table 2 Adverse events by dose and AUC of initial occurrence (dose=400 or ⩾600 mg bid; AUC<100 or ⩾100 mg l−1 h−1). (Fisher’s exact test)
From: Sorafenib in advanced melanoma: a critical role for pharmacokinetics?
All doses and AUC ( n =30) | Grade 3–4 | ||||||||
|---|---|---|---|---|---|---|---|---|---|
Adverse events | All grades | Grade 3–4 | Dose=400 mg bid ( n =30) | Dose ⩾600 mg bid ( n =19) | OR (95% CI) | P | AUC <100 ( n =27) | AUC ⩾100 ( n =15) | P |
HFSR | 23 (77%) | 12 (40%) | 8 (27%) | 4 (21%) | — | 0.7 | 8 (29%) | 2 (13%) | 0.3 |
Diarrhoea | 22 (73%) | 6 (20%) | 1 (3%) | 5 (26%) | 10 (2–71) | 0.03* | 5 (21%) | 1 (7%) | 0.4 |
Fatigue | 26 (87%) | 6 (20%) | 2 (7%) | 4 (21%) | — | 0.2 | 4 (14%) | 2 (13%) | 1 |
Anorexia | 13 (43%) | 6 (20%) | 1 (3%) | 5 (26%) | 10 (2–71) | 0.03* | 5 (18%) | 1 (7%) | 0.4 |
Cutaneous rash | 17 (57%) | 5 (17%) | 5 (17%) | 0 (0%) | — | 0.1 | 4 (18%) | 1 (7%) | 0.6 |
Hypertension | 19 (63%) | 3 (10%) | 2 (7%) | 1 (5%) | — | 1 | 1 (4%) | 2 (13%) | 0.3 |
Stomatitis | 6 (20%) | 3 (10%) | 2 (7%) | 1 (5%) | — | 1 | 3 (11%) | 0 (0%) | 0.5 |
Neutropenia | 5 (17%) | 3 (10%) | 2 (7%) | 1 (5%) | — | 1 | 3 (11%) | 0 (0%) | 0.5 |
Thrombocytopenia | 9 (30%) | 2 (7%) | 2 (7%) | 0 (0%) | — | 1 | 2 (7%) | 0 (0%) | 0.6 |
Anaemia | 8 (27%) | 1 (3%) | 1 (3%) | 0 (0%) | — | 1 | 1 (4%) | 0 (0%) | 1 |
Atrial fibrillation | 3 (10%) | 1 (3%) | 0 (0%) | 1 (5%) | — | 0.4 | 1 (4%) | 0 (0%) | 1 |
Proteinuria | 4 (13%) | 1 (3%) | 0 (0%) | 1 (5%) | — | 0.4 | 0 (0%) | 1 (7%) | 0.4 |
Hypothyroidism | 3 (10%) | 1 (3%) | 0 (0%) | 1 (5%) | — | 0.4 | 1 (4%) | 0 (0%) | 1 |
Pancreatitis | 1 (3%) | 1 (3%) | 0 (0%) | 1 (5%) | — | 0.4 | 1 (4%) | 0 (0%) | 1 |
Alopecia (grade 2) | 12 (40%) | 4 (13%) | 1 (3%) | 3 (16%) | — | 0.3 | 4 (14%) | 0 (0%) | 0.2 |
