Table 2:
Phase II and III ECOG-ACRIN Trials of 5FU and/or Capecitabine – Adverse Events reported in Trials with final Clinical Study Reports Available
| Study | Agent(s) | Number of patients included in AE analyses | Cardiac-ischemia or chest pain | Arrhythmias | LV Dysfunction/Heart Failure | Hypertension | Dyspnea | Thrombosis/thrombus/embolism | Other |
|---|---|---|---|---|---|---|---|---|---|
| E1103 | Capecitabine 1000mg/m2 twice daily + tipifarnib | n=68 | 11 (16%) | Thrombosis/embolism 1 (2%) | |||||
| E2200 | 5-FU 400mg/m2 weekly bolus irinotecan + leucovorin + bevacizumab | n=87 | Cardiac-ischemia 2 (2%) | Dysrhythmia 1 (1%) Palpitations 3 (3%) SVT 1 (1%) |
14 (16%) | 11(13%) | Cardiac other 1 (1%) | ||
| E2204 |
Capecitabine 825mg/m2 twice daily Arms A and B Arm A: cetuximab + gemcitabine Arm B: bevacizumab + gemcitabine |
n=130 | Chest pain 2 (2%) | SVT 2(2%) | LV diastolic dysfunction 1(1%) | 17 (13%) | 10 (8%) | 8(6%) | CP arrest, nonfatal 1(<1%) Pericardial effusion 1(<1 %) Cardiac other 1(<1%), |
| E2205 | 5-FU 180mg/m2 CI over 24 hours D 1–35 + oxaliplatin + cetuximab | Phase II n=22 |
Cardiac troponin 1 (5%) | Heart block/asystole 1(5%) Atrial fibrillation 1(5%) |
2 (9%) | 3 (14%) | Syncope 1(5%) | ||
| E3200 |
5FU 400mg/m2 bolus followed by 600mg/m2 CI over 22 hours in arms A and B A: oxaliplatin + leucovorin + bevacizumab B: oxaliplatin + leucovrin C: bevacizumab alone no 5FU |
n=808 | Cardiac ischemia 2(<1%) Cardiac troponin 3(<1%) Chest pain 8(<1%) |
SVT 6(<1%) | Cardiac left ventricular function 1(<1%) | 40 (5%) | Thrombosis/embolism 18(2%) |
Cardiac other 2(<1 %) | |
| E3201 |
5-FU bolus followed by CI 2400 mg/m2 over 46 hours adjuvant Arms A, B, D, and E Arms C and F 5FU bolus only |
n=177 (adjuvant portion) |
Cardiac-ischemia 1(<1%) | 2(1%) | 2(1%) | ||||
| E3204 | Capecitabine 825mg/m2 twice daily + oxaliplatin + bevacizumab + radiation then surgery, then adjuvant 5FU 400mg/m2 followed by 2400mg/m2 CI 46 hours + leucovorin +oxaliplatin + bevacizumab | n=55 | Chest/thoracic pain 2(4%) | 2 (4%) | 5(9%) | 2(4%) | Cardiac-other 1(2%) | ||
| E3205 |
5-FU 4000mg/m2 CI over 96 hours + cetuximab + cisplatin Arm 1: two cycles Arm 2: one cycle |
n=62 | Left ventricular systolic dysfunction 1(2%) | 1(2%) | 3(5%) | ||||
| E4203 |
5-FU 400mg/m2 bolus followed by 2400mg/m2 CI over 46 hours Arm B and C: leucovorin + oxaliplatin + bevacizumab Arm A: No 5FU irinotecan + oxaliplatin + bevacizumab |
n=205 | Cardiac-ischemia 1(<1%) Chest pain 3(1%) | Palpitations 3(2%)Atrial fibrillation 1(<1%) Arrhythmia other 2(1%) SVT 1 (<1%) | LV diastolic dysfunction 1(<1%) | 52 (25%) | 19(9%) | Sudden death 1(<1%) | |
| E5204 |
5FU 400 mg/m2 bolus followed by 2400mg/m2 CI over 46 hours Arm: A and B Arm B: + bevacizumab. |
n=347 | Cardiac-ischemia 2% Cardiac/heart pain 1% Chest pain 1 % |
Cardiomyopthy restrictive 1% | 3% | 4% |