title: Acute diarrhea during adjuvant therapy for rectal cancer: a detailed analysis from a randomized intergroup trial.
abstract: 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.
authors.affiliation: North Central Cancer Treatment Group, Coordinating Center, Rochester, MN, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Miller
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sargent
authors.forename: James A
authors.initials: JA
authors.lastname: Martenson
authors.forename: John S
authors.initials: JS
authors.lastname: Macdonald
authors.forename: Daniel
authors.initials: D
authors.lastname: Haller
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mayer
authors.forename: Leonard L
authors.initials: LL
authors.lastname: Gunderson
authors.forename: Tyvin A
authors.initials: TA
authors.lastname: Rich
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Cha
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Connell
mesh_terms: 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
chemical_list: D008130:Lomustine; D005472:Fluorouracil