Acute diarrhea during adjuvant therapy for rectal cancer: a detailed analysis from a randomized intergroup trial.
OBJECTIVE
During adjuvant radiotherapy (RT) for rectal cancer, patients receiving 5-fluorouracil (5-FU) by protracted venous infusion have a higher risk of diarrhea than have patients receiving bolus 5-FU. Toxicity from a previously reported randomized clinical trial was analyzed to quantify the difference in this risk. Additionally, the persistence of diarrhea after RT was analyzed.


METHODS
A total of 656 patients were eligible. Patients with T3-4 N0-2 M0 or T1-2 N1-2 M0 resected, high-risk rectal cancer were randomly allocated to receive 5-FU by either protracted venous infusion or bolus during RT (50.4-54.0 Gy). Two cycles of bolus 5-FU were given before and after RT. One-half of the first 445 patients were also randomly allocated to receive lomustine in conjunction with the bolus 5-FU. The incidence and severity of diarrhea in relation to patient and treatment characteristics were evaluated.


RESULTS
The rate of diarrhea was significantly greater in patients receiving 5-FU by protracted venous infusion than in patients receiving bolus 5-FU; the difference was most pronounced for Grade 3 (severe) diarrhea (21% versus 13%, p = 0.007). The incidence and magnitude of diarrhea before and after RT were similar. Patients treated with an anterior resection had a higher rate of severe or life-threatening diarrhea than did patients treated with an abdominoperineal resection (31% vs. 12%, p < 0.001).


CONCLUSIONS
During pelvic RT, patients who receive 5-FU by protracted venous infusion rather than by bolus have a higher risk of severe or life-threatening diarrhea during RT. This risk does not appear to persist during chemotherapy after completion of pelvic RT.
Miller
Robert C
RC
North Central Cancer Treatment Group, Coordinating Center, Rochester, MN, USA.
Sargent
Daniel J
DJ
Martenson
James A
JA
Macdonald
John S
JS
Haller
Daniel
D
Mayer
Robert J
RJ
Gunderson
Leonard L
LL
Rich
Tyvin A
TA
Cha
Stephen S
SS
O'Connell
Michael J
MJ
D000208:Acute Disease; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D003967:Diarrhea / Q000139:chemically induced / Q000209:etiology*; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D008130:Lomustine / Q000008:administration & dosage / Q000009:adverse effects; D009367:Neoplasm Staging; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery
D008130:Lomustine; D005472:Fluorouracil