title: Irinotecan is an active agent in untreated patients with metastatic colorectal cancer.
abstract: OBJECTIVE
  To determine the response rate, survival, and toxicity of the new anticancer agent, irinotecan (CPT-11), in the treatment of metastatic colorectal cancer.
  
  
  METHODS
  Forty-one chemotherapy-naive patients with measurable metastatic colorectal cancer were treated with a 90-minute infusion of irinotecan 125 mg/m2 administered weekly for 4 weeks every 6 weeks. Pretreatment tumor biopsies to assess topoisomerase-I (Topo-I) activity were obtained from 11 patients. The pharmacokinetics for irinotecan and its active metabolite, SN-38, were determined in 18 patients.
  
  
  RESULTS
  Thirteen of 41 patients (32%) had a partial response (PR; 95% confidence interval, 18% to 46%). The median response duration was 8.1 months (range, 4.0 to 16.0) and the median survival time was 12.1 months (range, 2.1 to 21.7) for all 41 patients. Grade 3 or 4 toxicities were diarrhea (29% of patients) and neutropenia (22% of patients). Grade 3 or 4 diarrhea was substantially more prevalent in the initial 18 patients on study, with an incidence rate of 56%; a significant reduction in the incidence of severe diarrhea to 9% was noted with strict adherence to an antidiarrheal regimen of loperamide and diphenyldramine. No correlations were seen between pharmacokinetics of irinotecan/SN-38 and the clinical parameters of response, survival, or incidence of diarrhea.
  
  
  CONCLUSIONS
  Irinotecan has activity in the treatment of patients with metastatic colorectal cancer. Strict adherence to an antidiarrheal regimen of diphenhydramine/loperamide significantly reduced the incidence of diarrhea; the agent was thereafter well tolerated in the majority of patients.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, New York, NY, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Conti
authors.forename: N E
authors.initials: NE
authors.lastname: Kemeny
authors.forename: L B
authors.initials: LB
authors.lastname: Saltz
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.forename: W P
authors.initials: WP
authors.lastname: Tong
authors.forename: T C
authors.initials: TC
authors.lastname: Chou
authors.forename: M
authors.initials: M
authors.lastname: Sun
authors.forename: S
authors.initials: S
authors.lastname: Pulliam
authors.forename: C
authors.initials: C
authors.lastname: Gonzalez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D012004:Rectal Neoplasms / Q000188:drug therapy*; D012074:Remission Induction; D016019:Survival Analysis
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin