Table 3.
Worst Grade of Toxicity per Patient by Arm in NSABP R-03 Trial According to National Cancer Institute Common Toxicity Criteria, Version 1.0
| Toxicity | Any Toxicity (%) |
Grade 3, 4, or 5 (%) |
Grade 4 or 5 (%)* |
|||
|---|---|---|---|---|---|---|
| Preoperative Arm(n = 126) | Postoperative Arm(n = 99) | Preoperative Arm(n = 126) | Postoperative Arm(n = 99) | Preoperative Arm(n = 126) | Postoperative Arm(n = 99) | |
| Overall toxicity | 99 | 97 | 52 | 49 | 33 | 23 |
| Diarrhea | 82 | 88 | 36 | 29 | 24 | 14 |
| Nausea | 66 | 59 | 12 | 7 | NA | NA |
| Vomiting | 31 | 28 | 7 | 8 | 3 | 3 |
| Stomatitis | 30 | 27 | 3 | 3 | 1 | 2 |
| Leukopenia | 71 | 68 | 10 | 8 | 2 | 1 |
| Granulocytopenia | 52 | 52 | 13 | 15 | 3 | 4 |
NOTE. In National Cancer Institute Common Toxicity Criteria, Version 1.0, grade 3 diarrhea was defined as an increase of seven to nine stools over baseline every 24 hours (severe). Grade 4 diarrhea was defined as having 10 or more stools per day, grossly bloody diarrhea, or need for parenteral support.
Abbreviations: NSABP R-03, National Surgical Adjuvant Breast and Bowel Project R-03; NA, not applicable.
Deaths within 30 days of last chemotherapy dose or random assignment occurred in 5% of preoperative patients and 3% of postoperative patients. However, several of these deaths appeared to be unrelated to treatment. Probable or possible treatment-related mortality was 3% for preoperative and 1% for postoperative patients. A total of nine deaths occurred within 30 days of random assignment or last dose of chemotherapy administration; four deaths did not appear to be related to protocol therapy. Other deaths comprised two patients with a history of severe coronary artery disease who experienced cardiac arrest with no evidence of chemotherapy adverse effects, one patient with a dissecting thoracic aortic aneurysm, and one patient who died postoperatively of aspiration pneumonia who had not received any chemotherapy. The number of deaths considered possibly or probably related to protocol therapy were four (3.2%) of 126 in the preoperative group; two were due to complications from chemotherapy-induced dehydration related to diarrhea, nausea, and/or vomiting; one was due to perforated sigmoid colon in a patient with fixation of the bowel to a large rectal tumor; one was due to postoperative acute respiratory distress syndrome and peritonitis. In the postoperative group, the only death (one [1%] of 99) was due to dehydration related to chemotherapy-induced diarrhea, nausea, and vomiting. We believe these rates of treatment-related fatality are within the acceptable range for combined modality adjuvant therapy of high-risk rectal cancer in clinical practice. Clinicians should be aware of the potential for severe diarrhea, nausea, and vomiting, which can lead to dehydration; should monitor patients carefully, particularly during radiation therapy; and should treat dehydration aggressively with intravenous fluids.