title: Phase II trial of irinotecan in patients with progressive or rapidly recurrent colorectal cancer.
abstract: OBJECTIVE
  To evaluate irinotecan (CPT-11; Yakult Honsha, Tokyo, Japan) in patients with metastatic colorectal carcinoma that had recurred or progressed following fluorouracil (5-FU)-based therapy.
  
  
  METHODS
  Patients were treated with irinotecan 125 to 150 mg/m2 intravenously (IV) every week for 4 weeks, followed by a 2-week rest. Forty-eight patients were entered onto the study and all were assessable for toxicity. Forty-three patients completed one full course of therapy and were assessable for response.
  
  
  RESULTS
  One complete and nine partial responses were observed (response rate, 23%; 95% confidence interval [CI], 10% to 36%). The median response duration was 6 months (range, 2 to 13). The median survival time was 10.4 months and the 1-year survival rate was 46% (95% CI, 39% to 53%). Grade 4 diarrhea occurred in four of the first nine patients (44%) treated on this study at the 150-mg/m2 dose level. The study was amended to reduce the starting dose of irinotecan to 125 mg/m2. At this dose, nine of 39 patients (23%) developed grade 4 diarrhea. Aggressive administration of loperamide also reduced the incidence of grade 4 diarrhea. Grade 4 neutropenia occurred in eight of 48 patients (17%), but was associated with bacteremia and sepsis in only case.
  
  
  CONCLUSIONS
  Irinotecan has significant single-agent activity against colorectal cancer that has progressed during or shortly after treatment with 5-FU-based chemotherapy. The incidence of severe diarrhea is reduced by using a starting dose of irinotecan 125 mg/m2 and by initiating loperamide at the earliest signs of diarrhea. These results warrant further clinical evaluation to define the role of irinotecan in the treatment of individuals with colorectal cancer.
authors.affiliation: University of Texas Health Science Center at San Antonio, TX, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Rothenberg
authors.forename: J R
authors.initials: JR
authors.lastname: Eckardt
authors.forename: J G
authors.initials: JG
authors.lastname: Kuhn
authors.forename: H A
authors.initials: HA
authors.lastname: Burris
authors.forename: J
authors.initials: J
authors.lastname: Nelson
authors.forename: S G
authors.initials: SG
authors.lastname: Hilsenbeck
authors.forename: G I
authors.initials: GI
authors.lastname: Rodriguez
authors.forename: A M
authors.initials: AM
authors.lastname: Thurman
authors.forename: L S
authors.initials: LS
authors.lastname: Smith
authors.forename: S G
authors.initials: SG
authors.lastname: Eckhardt
authors.forename: G R
authors.initials: GR
authors.lastname: Weiss
authors.forename: G L
authors.initials: GL
authors.lastname: Elfring
authors.forename: D A
authors.initials: DA
authors.lastname: Rinaldi
authors.forename: L J
authors.initials: LJ
authors.lastname: Schaaf
authors.forename: D D
authors.initials: DD
authors.lastname: Von Hoff
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D000930:Antidiarrheals / Q000627:therapeutic use; 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; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced / Q000188:drug therapy; D018450:Disease Progression; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008139:Loperamide / Q000627:therapeutic use; D016879:Salvage Therapy; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000930:Antidiarrheals; D000972:Antineoplastic Agents, Phytogenic; D008139:Loperamide; D000077146:Irinotecan; D002166:Camptothecin