title: Phase II study of activated charcoal to prevent irinotecan-induced diarrhea.
abstract: OBJECTIVE
  The dose-limiting toxicity of irinotecan (CPT-11; Camptosar) is delayed-onset diarrhea, with an incidence at the grade 3 to 4 level of 20% to 35%. SN38, its active moiety, is responsible by a direct effect on mucosal topoisomerase-I. The aim of this study was to assess whether activated charcoal (AC), possibly by adsorbing free lumenal SN38, can reduce irinotecan-induced diarrhea (CID) and optimize its dose-intensity.
  
  
  METHODS
  Patients with advanced colorectal cancer receiving irinotecan 125 mg/m(2) intravenously once a week for 4 weeks every 6 weeks were studied. In cycle 1, patients received irinotecan plus AC (5 mL aqueous Charcodote [1,000 mg AC] plus 25 mL water) given the evening before the irinotecan dose and then tid for 48 hours after the dose. In cycle 2, no AC was given. National Cancer Institute Common Toxicity Criteria diarrhea grade, irinotecan dose-intensity, and loperamide consumption were recorded prospectively in both cycles.
  
  
  RESULTS
  Twenty-eight patients had completed cycle 1 with AC; 24 subsequently completed cycle 2 without AC. Grade 3 to 4 diarrhea was 7.1% v 25%, and grade 0 diarrhea was 46.4% v 20.8% in cycles 1 and 2, respectively. Median percent planned dose delivered was 98% v 70% in cycles 1 and 2, respectively. In cycles 1 and 2, respectively, 25% v 54% patients took more than 10 loperamide tablets. AC was well tolerated with excellent compliance.
  
  
  CONCLUSIONS
  The administration of AC with irinotecan reduced the incidence of grade 3 to 4 diarrhea and antidiarrheal medication consumption and increased irinotecan dose-intensity. Prophylactic AC may have a role in reducing dose-limiting CID and optimizing irinotecan therapy.
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Ontario, Canada. Michael.Michael@petermac.org
authors.forename: Michael
authors.initials: M
authors.lastname: Michael
authors.forename: MaryAnne
authors.initials: M
authors.lastname: Brittain
authors.forename: Jane
authors.initials: J
authors.lastname: Nagai
authors.forename: Ronald
authors.initials: R
authors.lastname: Feld
authors.forename: David
authors.initials: D
authors.lastname: Hedley
authors.forename: Amit
authors.initials: A
authors.lastname: Oza
authors.forename: Lillian
authors.initials: L
authors.lastname: Siu
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Moore
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D002166:Camptothecin / Q000009:adverse effects* / Q000031:analogs & derivatives*; D002606:Charcoal / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced* / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002606:Charcoal; D000077146:Irinotecan; D002166:Camptothecin