Table 2.
Treatment-emergent adverse events arising in ≥10% patients, or of special interest, irrespective of cause
|
Cediranib group (N=62) |
Placebo group (N=62) |
p value* | |||
|---|---|---|---|---|---|
| Grade 1–2 | Grade 3–4 | Grade 1–2 | Grade 3–4 | ||
| Haematological adverse events | |||||
| Anaemia | 51 (82%) | 8 (13%) | 49 (79%) | 8 (13%) | 0·99 |
| Platelet count decreased | 34 (55%) | 10 (16%) | 28 (45%) | 4 (6%) | 0·09 |
| White blood cell decreased | 28 (45%) | 15 (24%) | 32 (52%) | 7 (11%) | 0·06 |
| Neutrophil count decreased | 22 (35%) | 26 (42%) | 20 (32%) | 23 (37%) | 0·58 |
| Any haematological adverse event | 13 (21%) | 49 (79%) | 12 (19%) | 49 (79%) | 0·99 |
| Liver function adverse events | |||||
| Increased alanine aminotransferase | 43 (69%) | 7 (11%) | 39 (63%) | 4 (6%) | 0·34 |
| Increased alkaline phosphatase | 43 (69%) | 4 (6%) | 43 (69%) | 4 (6%) | 0·99 |
| Increased aspartate aminotransferase | 40 (65%) | 3 (5%) | 35 (56%) | 2 (3%) | 0·65 |
| Increased gamma-glutamyl transpeptidase | 32 (52%) | 29 (47%) | 23 (37%) | 31 (50%) | 0·72 |
| Increased blood bilirubin | 9 (15%) | 3 (5%) | 9 (15%) | 4 (6%) | 0·70 |
| Non-haematological adverse events | |||||
| Constipation | 42 (68%) | 0 (0%) | 42 (68%) | 0 (0%) | .. |
| Anorexia | 40 (65%) | 3 (5%) | 25 (40%) | 2 (3%) | .. |
| Nausea | 39 (63%) | 4 (6%) | 42 (68%) | 1 (2%) | .. |
| Diarrhoea | 37 (60%) | 8 (13%) | 22 (35%) | 2 (3%) | 0·05 |
| Fatigue | 36 (58%) | 16 (26%) | 40 (65%) | 7 (11%) | 0·04 |
| Lethargy | 35 (56%) | 8 (13%) | 35 (56%) | 7 (11%) | 0·78 |
| Hypoalbuminaemia | 31 (50%) | 0 (0%) | 23 (37%) | 0 (0%) | .. |
| Abdominal pain | 28 (45%) | 4 (6%) | 27 (44%) | 5 (8%) | .. |
| Hyponatraemia | 26 (42%) | 10 (16%) | 28 (45%) | 4 (6%) | 0·09 |
| Hypercalcaemia | 25 (40%) | 2 (3%) | 22 (35%) | 0 (0%) | .. |
| Vomiting | 24 (39%) | 6 (10%) | 21 (34%) | 9 (15%) | 0·41 |
| Hypomagnesaemia | 23 (37%) | 7 (11%) | 18 (29%) | 3 (5%) | 0·19 |
| Mucositis oral | 23 (37%) | 2 (3%) | 13 (21%) | 0 (0%) | .. |
| Hypophosphataemia | 23 (37%) | 2 (3%) | 17 (27%) | 2 (3%) | .. |
| Oedema limbs | 22 (35%) | 0 (0%) | 16 (26%) | 1 (2%) | .. |
| Pain | 22 (35%) | 8 (13%) | 25 (40%) | 4 (6%) | 0·22 |
| Dysgeusia | 20 (32%) | 0 (0%) | 19 (31%) | 0 (0%) | .. |
| Hypokalaemia | 20 (32%) | 1 (2%) | 18 (29%) | 0 (0%) | .. |
| Hypertension | 19 (31%) | 23 (37%) | 17 (27%) | 13 (21%) | 0·05 |
| Creatinine increased | 17 (27%) | 0 (0%) | 10 (16%) | 0 (0%) | .. |
| Peripheral sensory neuropathy | 15 (24%) | 1 (2%) | 16 (26%) | 0 (0%) | .. |
| Fever | 15 (24%) | 3 (5%) | 14 (23%) | 1 (2%) | .. |
| Dyspnoea | 15 (24%) | 1 (2%) | 16 (26%) | 3 (5%) | .. |
| Epistaxis | 15 (24%) | 2 (3%) | 6 (10%) | 0 (0%) | .. |
| Dry mouth | 14 (23%) | 1 (2%) | 8 (13%) | 0 (0%) | .. |
| Upper respiratory infection | 14 (23%) | 1 (2%) | 5 (8%) | 4 (6%) | .. |
| Cough | 13 (21%) | 0 (0%) | 8 (13%) | 0 (0%) | .. |
| Dyspepsia | 13 (21%) | 0 (0%) | 7 (11%) | 0 (0%) | .. |
| Flu-like symptoms | 12 (19%) | 0 (0%) | 12 (19%) | 0 (0%) | .. |
| Back pain | 12 (19%) | 3 (5%) | 10 (16%) | 1 (2%) | .. |
| Generalised muscle weakness | 12 (19%) | 1 (2%) | 6 (10%) | 0 (0%) | .. |
| Rash maculopapular | 12 (19%) | 0 (0%) | 5 (8%) | 1 (2%) | .. |
| Sore throat | 11 (18%) | 0 (0%) | 6 (10%) | 0 (0%) | .. |
| Weight loss | 11 (18%) | 1 (2%) | 4 (6%) | 0 (0%) | .. |
| Gastro-oesophageal reflux disease | 10 (16%) | 0 (0%) | 17 (27%) | 0 (0%) | .. |
| Insomnia | 10 (16%) | 1 (2%) | 12 (19%) | 0 (0%) | .. |
| Alopecia | 10 (16%) | 0 (0%) | 18 (29%) | 0 (0%) | .. |
| Urinary tract infection | 9 (15%) | 0 (0%) | 5 (8%) | 2 (3%) | .. |
| Pain in extremity | 8 (13%) | 0 (0%) | 5 (8%) | 1 (2%) | .. |
| Myalgia | 7 (11%) | 0 (0%) | 11 (18%) | 0 (0%) | .. |
| Papulopustular rash | 7 (11%) | 0 (0%) | 3 (5%) | 0 (0%) | .. |
| Flatulence | 7 (11%) | 0 (0%) | 6 (10%) | 0 (0%) | .. |
| Dizziness | 6 (10%) | 0 (0%) | 8 (13%) | 0 (0%) | .. |
| Mucosal infection | 6 (10%) | 0 (0%) | 2 (3%) | 0 (0%) | .. |
| Chills | 5 (8%) | 0 (0%) | 2 (3%) | 0 (0%) | .. |
| Biliary tract infection | 3 (5%) | 5 (8%) | 0 (0%) | 3 (5%) | .. |
| Tinnitus | 3 (5%) | 1 (2%) | 9 (15%) | 0 (0%) | .. |
| Hearing impaired | 2 (3%) | 1 (2%) | 7 (11%) | 0 (0%) | .. |
| Lung infection | 2 (3%) | 2 (3%) | 9 (15%) | 2 (3%) | .. |
| Sepsis | 1 (2%) | 5 (8%) | 1 (2%) | 2 (3%) | .. |
| Thromboembolic event | 0 (0%) | 7 (11%) | 1 (2%) | 8 (13%) | 0·78 |
| Febrile neutropenia | 0 (0%) | 4 (6%) | 0 (0%) | 1 (2%) | .. |
| Myocardial Infarction | 0 (0%) | 1 (2%) | 0 (0%) | 0 (0%) | .. |
| Non-cardiac chest pain | 0 (0%) | 2 (3%) | 6 (10%) | 0 (0%) | .. |
| Hepatobiliary disorder—biliary obstruction | 0 (0%) | 0 (0%) | 0 (0%) | 4 (6%) | .. |
| Hepatic infection | 0 (0%) | 0 (0%) | 0 (0%) | 1 (2%) | .. |
Data are n (%).
†Five patients had a grade 5 adverse event, three in the cediranib group (one myocardial infarction, one cerebrovascular accident, one gastric haemorrhage) and two in the placebo group (one cholangitis, one peripheral ischaemia).
*
Comparison of incidence of grade 3–4 events in at least ten patients (Pearson's χ2 test).