Table 3.
Adverse events during cycles one to four of chemotherapy among patients in the quality-of-life and toxicity substudy
|
Standard epirubicin (n=1070) |
Accelerated epirubicin (n=1045) |
p value for trend* | p value for events grade ≥3 | |||||
|---|---|---|---|---|---|---|---|---|
| Grade 1–2 | Grade 3 | Grade 4 | Grade 1–2 | Grade 3 | Grade 4 | |||
| Events prespecified on case report form | ||||||||
| Fatigue | 919 (86%) | 52 (5%) | 4 (<0·5%) | 889 (85%) | 62 (6%) | 1 (<0·5%) | 0·16 | 0·45 |
| Nausea | 806 (75%) | 19 (2%) | 1 (<0·5%) | 801 (77%) | 23 (2%) | 0 | 0·24 | 0·65 |
| Vomiting | 361 (34%) | 23 (2%) | 1 (<0·5%) | 338 (32%) | 20 (2%) | 2 (<0·5%) | 0·47 | 0·88 |
| Alopecia† | 1023 (96%) | 0 | 0 | 995 (95%) | 0 | 0 | 0·43 | .. |
| Neuropathy | 132 (12%) | 1 (<0·5%) | 0 | 113 (11%) | 2 (<0·5%) | 0 | 0·27 | 0·62 |
| Mucositis/stomatitis | 723 (68%) | 10 (1%) | 0 | 718 (69%) | 13 (1%) | 0 | 0·66 | 0·53 |
| Hand–foot syndrome | 36 (3%) | 0 | 0 | 80 (8%) | 9 (1%) | 0 | <0·0001 | 0·0017 |
| Skin | 291 (27%) | 3 (<0·5%) | 0 | 309 (30%) | 4 (<0·5%) | 0 | 0·084 | 0·72 |
| Superficial thrombophlebitis† | 247 (23%) | 0 | 0 | 232 (22%) | 0 | 0 | 0·63 | .. |
| Diarrhoea | 324 (30%) | 11 (1%) | 0 | 359 (34%) | 14 (1%) | 0 | 0·061 | 0·55 |
| Constipation | 696 (65%) | 7 (1%) | 0 | 695 (67%) | 4 (<0·5%) | 0 | 0·46 | 0·55 |
| Infection | 330 (31%) | 34 (3%) | 4 (<0·5%) | 296 (28%) | 33 (3%) | 1 (<0·5%) | 0·18 | 0·72 |
| Anaemia | 264 (25%) | 0 | 0 | 421 (40%) | 1 (<0·5%) | 0 | <0·0001 | 0·49 |
| Leucopenia | 276 (26%) | 37 (3%) | 4 (<0·5%) | 35 (3%) | 8 (1%) | 2 (<0·5%) | <0·0001 | <0·0001 |
| Neutropenia | 318 (30%) | 125 (12%) | 50 (5%) | 46 (4%) | 11 (1%) | 7 (1%) | <0·0001 | <0·0001 |
| Thrombocytopenia | 11 (1%) | 1 (<0·5%) | 1 (<0·5%) | 30 (3%) | 0 | 0 | 0·10 | 0·50 |
| Febrile neutropenia | 0 | 34 (3%) | 4 (<0·5%) | 0 | 14 (1%) | 1 (<0·5%) | 0·0019 | 0·002 |
| Other adverse events‡ | ||||||||
| Alanine aminotransferase increased | 20 (2%) | 1 (<0·5%) | 0 | 50 (5%) | 2 (<0·5%) | 0 | 0·00018 | 0·62 |
| Arthralgia | 30 (3%) | 1 (<0·5%) | 0 | 58 (6%) | 2 (<0·5%) | 0 | 0·0022 | 0·62 |
| Back pain | 22 (2%) | 0 | 0 | 40 (4%) | 1 (<0·5%) | 0 | 0·0028 | 0·49 |
| Blood alkaline phosphatase | 0 | 0 | 0 | 8 (1%) | 0 | 0 | 0·0017 | .. |
| Blood alkaline phosphatase increased | 4 (<0·5%) | 0 | 0 | 33 (3%) | 0 | 0 | <0·0001 | .. |
| Cough | 53 (5%) | 0 | 0 | 68 (7%) | 1 (<0·5%) | 0 | 0·17 | 0·49 |
| Dry eye | 33 (3%) | 0 | 0 | 17 (2%) | 0 | 0 | 0·023 | .. |
| Dry mouth | 44 (4%) | 0 | 0 | 57 (5%) | 1 (<0·5%) | 0 | 0·11 | 0·49 |
| Dysgeusia | 146 (14%) | 1 (<0·5%) | 0 | 165 (16%) | 1 (<0·5%) | 0 | 0·20 | >0·99 |
| Dyspepsia | 234 (22%) | 1 (<0·5%) | 0 | 268 (26%) | 3 (<0·5%) | 0 | 0·078 | 0·37 |
| Epistaxis | 7 (1%) | 0 | 0 | 22 (2%) | 0 | 0 | 0·0039 | .. |
| Haemorrhoids | 10 (1%) | 0 | 0 | 25 (2%) | 0 | 0 | 0·0066 | .. |
| Headache | 97 (9%) | 5 (<0·5%) | 0 | 114 (11%) | 2 (<0·5%) | 0 | 0·14 | 0·45 |
| Lacrimation increased | 67 (6%) | 0 | 0 | 89 (9%) | 0 | 0 | 0·10 | .. |
| Liver function test abnormal | 27 (3%) | 3 (<0·5%) | 0 | 41 (4%) | 3 (<0·5%) | 0 | 0·10 | >0·99 |
| Lymphoedema | 23 (2%) | 2 (<0·5%) | 0 | 11 (1%) | 0 | 0 | 0·028 | 0·50 |
| Oropharyngeal pain | 42 (4%) | 1 (<0·5%) | 1 (<0·5%) | 53 (5%) | 1 (<0·5%) | 0 | 0·23 | >0·99 |
| Tearfulness | 0 | 0 | 0 | 6 (1%) | 0 | 0 | 0·0071 | .. |
Adverse events were graded with the Common Terminology Criteria for Adverse Events version 3.0. Events are shown that meet at least one one of the following criteria: difference in proportion of patients reporting an event of any grade is >1% between the epirubicin groups; the proportion of patients experiencing an event of any grade is >10% in either the standard epirubicin or the accelerated epirubicin group; and the difference between epirubicin groups in the proportion of patients experiencing an event of any grade is significant (p<0·01). No patients died from these events (grade 5).
Trend tests combine grade 3–5 adverse events.
Common Terminology Criteria for Adverse Events grades 3 and 4 are not applicable.
Free-text preferred terms of Medical Dictionary for Regulatory Activities version 10 are used.