Table 4.
Adverse events during cycles five to eight of chemotherapy among patients in the quality-of-life and toxicity substudy
|
CMF (n=1030) |
Capecitabine (n=1044) |
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 | 825 (80%) | 107 (10%) | 2 (<0·5%) | 773 (74%) | 52 (5%) | 0 | <0·0001 | <0·0001 |
| Nausea | 675 (66%) | 21 (2%) | 2 (<0·5%) | 548 (52c%) | 7 (1%) | 0 | <0·0001 | 0·0029 |
| Vomiting | 303 (29%) | 23 (2%) | 0 | 203 (19%) | 14 (1%) | 1 (<0·5%) | <0·0001 | 0·19 |
| Alopecia† | 963 (93%) | 0 | 0 | 902 (86%) | 0 | 0 | <0·0001 | .. |
| Neuropathy | 162 (16%) | 2 (<0·5%) | 0 | 225 (22%) | 2 (<0·5%) | 1 (<0·5%) | 0·00027 | >0·99 |
| Mucositis/stomatitis | 617 (60%) | 48 (5%) | 4 (<0·5%) | 426 (41%) | 9 (1%) | 1 (<0·5%) | <0·0001 | <0·0001 |
| Hand–foot syndrome | 118 (11%) | 3 (<0·5%) | 0 | 649 (62%) | 129 (12%) | 0 | <0·0001 | <0·0001 |
| Skin | 209 (20%) | 0 | 0 | 289 (28%) | 4 (<0·5%) | 0 | 0·89 | 0·12 |
| Thrombosis/embolism | 16 (2%) | 14 (1%) | 7 (1%) | 14 (1%) | 5 (<0·5%) | 2 (<0·5%) | 0·014 | 0·0074 |
| Superficial thrombophlebitis† | 162 (16%) | 0 | 0 | 144 (14%) | 0 | 0 | 0·21 | .. |
| Diarrhoea | 434 (42%) | 44 (4%) | 2 (<0·5%) | 490 (47%) | 63 (6%) | 4 (<0·5%) | 0·0069 | 0·053 |
| Constipation | 476 (46%) | 4 (<0·5%) | 0 | 189 (18%) | 2 (<0·5%) | 0 | <0·0001 | 0·45 |
| Infection | 260 (25%) | 96 (9%) | 6 (1%) | 200 (19%) | 18 (2%) | 0 | <0·0001 | <0·0001 |
| Anaemia | 411 (40%) | 29 (3%) | 1 (<0·5%) | 250 (24%) | 4 (<0·5%) | 2 (<0·5%) | <0·0001 | <0·0001 |
| Leucopenia | 376 (37%) | 95 (9%) | 80 (8%) | 136 (13%) | 7 (1%) | 1 (<0·5%) | <0·0001 | <0·0001 |
| Neutropenia | 263 (26%) | 155 (15%) | 166 (16%) | 165 (16%) | 17 (2%) | 6 (1%) | <0·0001 | <0·0001 |
| Thrombocytopenia | 109 (11%) | 13 (1%) | 3 (<0·5%) | 32 (3%) | 1 (<0·5%) | 1 (<0·5%) | <0·0001 | 0·0065 |
| Febrile Neutropenia | 0 | 96 (9%) | 19 (2%) | 0 | 7 (1%) | 1 (<0·5%) | <0·0001 | <0·0001 |
| Other adverse events‡ | ||||||||
| Abdominal pain | 24 (2%) | 0 | 0 | 33 (3%) | 3 (<0·5%) | 0 | 0·15 | 0·25 |
| Alanine aminotransferase increased | 54 (5%) | 2 (<0·5%) | 1 (<0·5%) | 33 (3%) | 3 (<0·5%) | 0 | 0·026 | >0·99 |
| Arthralgia | 56 (5%) | 0 | 0 | 39 (4%) | 0 | 0 | 0·074 | .. |
| Blood bilirubin | 0 | 0 | 0 | 9 (1%) | 0 | 0 | 0·0038 | .. |
| Chest pain | 5 (<0·5%) | 0 | 0 | 15 (1%) | 3 (<0·5%) | 0 | 0·010 | 0·25 |
| Chills | 14 (1%) | 0 | 0 | 1 (<0·5%) | 0 | 0 | 0·00046 | .. |
| Cough | 50 (5%) | 0 | 0 | 37 (4%) | 0 | 0 | 0·15 | .. |
| Dry mouth | 60 (6%) | 1 (<0·5%) | 0 | 80 (8%) | 1 (<0·5%) | 0 | 0·10 | >0·99 |
| Dysgeusia | 112 (11%) | 2 (<0·5%) | 0 | 116 (11%) | 0 | 0 | >0·99 | 0·25 |
| Dyspepsia | 107 (10%) | 0 | 0 | 78 (8%) | 0 | 0 | 0·021 | .. |
| Dyspnoea | 66 (6%) | 7 (1%) | 2 (<0·5%) | 31 (3%) | 1 (<0·5%) | 2 (<0·5%) | <0·0001 | 0·089 |
| Epistaxis | 28 (3%) | 0 | 0 | 10 (1%) | 0 | 0 | 0·0029 | .. |
| Eye pain | 39 (4%) | 0 | 0 | 17 (2%) | 0 | 0 | 0·0027 | .. |
| Foreign body sensation in eyes | 29 (3%) | 0 | 0 | 9 (1%) | 0 | 0 | 0·00090 | .. |
| Hot flush | 94 (9%) | 1 (<0·5%) | 1 (<0·5%) | 55 (5%) | 0 | 0 | 0·00038 | 0·25 |
| Insomnia | 42 (4%) | 0 | 0 | 24 (2%) | 2 (<0·5%) | 0 | 0·048 | 0·50 |
| Lacrimation increased | 81 (8%) | 0 | 0 | 52 (5%) | 1 (<0·5%) | 0 | 0·012 | >0·99 |
| Lymphoedema | 31 (3%) | 0 | 0 | 19 (2%) | 0 | 0 | 0·086 | .. |
| Nasopharyngitis | 32 (3%) | 0 | 0 | 13 (1%) | 0 | 0 | 0·0039 | .. |
| Non-cardiac chest pain | 6 (1%) | 2 (<0·5%) | 0 | 11 (1%) | 7 (1%) | 1 (<0·5%) | 0·051 | 0·11 |
| Oral candidiasis | 13 (1%) | 1 (<0·5%) | 0 | 1 (<0·5%) | 0 | 0 | 0·00046 | 0·50 |
| Pyrexia | 38 (4%) | 0 | 0 | 14 (1%) | 0 | 0 | 0·00064 | .. |
| Vision blurred | 11 (1%) | 0 | 0 | 1 (<0·5%) | 0 | 0 | 0·0032 | .. |
Adverse events were graded with the Common Terminology Criteria for Adverse Events version 3.0. Events are shown that meet at least one of the following criteria: difference in proportion of patients reporting an event of any grade is >1% between the CMF and capecitabine groups; the proportion of patients experiencing an event of any grade is >10% in either the CMF or capecitabine group; and the difference between the CMF and capecitabine groups in the proportion of patients experiencing an event of any grade is significant (p<0·01). Three substudy patients in the CMF group died from infections (grade 5 adverse events). Table 2 shows cause of death data for the whole cohort. CMF=cyclophosphamide, methotrexate, and fluorouracil.
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.