title: Phase II trial of irinotecan in patients with metastatic colorectal carcinoma.
abstract: OBJECTIVE
  To evaluate the objective tumor response rate and toxicities of patients with metastatic colorectal carcinoma treated with irinotecan hydrochloride (CPT-11).
  
  
  METHODS
  A total of 121 patients with advanced colorectal carcinoma--90 with prior fluorouracil (5-FU) exposure and 31 chemotherapeutically naive patients--were enrolled between May 1993 and June 1994. Patients were treated with CPT-11 at 125 mg/m2 intravenously weekly for 4 weeks followed by a 2-week rest.
  
  
  RESULTS
  Among 90 patients with prior 5-FU chemotherapy, 12 partial responses were observed (response rate, 13.3%; 95% confidence interval [CI], 7.1% to 22.1%). Among 31 chemotherapy-naive patients, eight had partial responses (response rate, 25.8%; 95% CI, 11.9% to 44.6%). The median response duration as measured from time of initial treatment for the two groups was 7.7 months and 7.6 months, respectively. The major adverse reactions were gastrointestinal and hematologic. The incidence of grade 3 or 4 diarrhea was 36.4%, while the overall incidence of grade 3 or 4 leukopenia was 21.5% of patients. Only four of 121 patients (3.3%) developed neutropenic fever (grade 4 neutropenia with > or = grade 2 fever). The incidence of grade 4 leukopenia was higher in patients with prior pelvic radiotherapy (chi2 test P = .04), while the incidence of grade 3 or 4 diarrhea demonstrated no association with previous pelvic irradiation.
  
  
  CONCLUSIONS
  According to the study design, CPT-11 showed promising activity in chemotherapy-naive patients with advanced colorectal carcinoma and modest activity in patients with prior 5-FU exposure. The toxicity with this schedule appears manageable with appropriate dose modification for individual patient tolerance and an intensive loperamide regimen for the management of diarrhea. Care should be taken when treating patients with prior pelvic radiotherapy because of the increased risk of neutropenia.
authors.affiliation: Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. pitot.henry@mayo.edu
authors.forename: H C
authors.initials: HC
authors.lastname: Pitot
authors.forename: D B
authors.initials: DB
authors.lastname: Wender
authors.forename: M J
authors.initials: MJ
authors.lastname: O'Connell
authors.forename: G
authors.initials: G
authors.lastname: Schroeder
authors.forename: R M
authors.initials: RM
authors.lastname: Goldberg
authors.forename: J
authors.initials: J
authors.lastname: Rubin
authors.forename: J A
authors.initials: JA
authors.lastname: Mailliard
authors.forename: J A
authors.initials: JA
authors.lastname: Knost
authors.forename: C
authors.initials: C
authors.lastname: Ghosh
authors.forename: R J
authors.initials: RJ
authors.lastname: Kirschling
authors.forename: R
authors.initials: R
authors.lastname: Levitt
authors.forename: H E
authors.initials: HE
authors.lastname: Windschitl
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin