title: A phase II, randomized, double blind trial of calcium aluminosilicate clay versus placebo for the prevention of diarrhea in patients with metastatic colorectal cancer treated with irinotecan.
abstract: OBJECTIVE
  Calcium aluminosilicate clay (CASAD) is a naturally occurring clay that serves as a cation exchange absorbent. We hypothesized that oral administration of CASAD would reduce the rate of grade 3/4 diarrhea associated with irinotecan use for metastatic colorectal cancer (CRC) by adsorbing the SN-38 metabolite.
  
  
  METHODS
  Patients receiving irinotecan-based chemotherapy were randomized equally between CASAD and placebo arms in this multicenter trial in order to assess differences in the proportions of patients with grade 3/4 diarrhea within 6 weeks. Additionally, we compared symptom severity between the two arms using the M.D. Anderson Symptom Inventory.
  
  
  RESULTS
  Between May 2009 and May 2012, 100 patients were enrolled. In evaluable patients, 7 of 43 (16 %) on the CASAD arm compared to 3 of 32 (9 %) on the placebo arm experienced grade 3/4 diarrhea (P = 0.70). The rate of any diarrhea among all patients was similar (CASAD arm, 64 % vs. placebo arm, 70 %). The rate of study dropout was 14 % in the CASAD arm and 38 % in the placebo arm (P = 0.01). No differences were found in symptom severity, individual symptom items, and in serious adverse events between the two arms.
  
  
  CONCLUSIONS
  Compared to placebo, CASAD use was safe but ineffective in preventing diarrhea in metastatic CRC patients treated with irinotecan-containing chemotherapy regimens. There were no distinct signals in terms of patient symptoms between arms, but there was significantly more patient dropout in the placebo arm. Future CASAD trials will focus on the active treatment of diarrhea.
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0426, Houston, TX, 77030, USA, bkkee@mdanderson.org.
authors.forename: Bryan K
authors.initials: BK
authors.lastname: Kee
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Morris
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Slack
authors.forename: Todd
authors.initials: T
authors.lastname: Crocenzi
authors.forename: Lucas
authors.initials: L
authors.lastname: Wong
authors.forename: Ben
authors.initials: B
authors.lastname: Esparaz
authors.forename: Michael
authors.initials: M
authors.lastname: Overman
authors.forename: Katrina
authors.initials: K
authors.lastname: Glover
authors.forename: Desiree
authors.initials: D
authors.lastname: Jones
authors.forename: Sijin
authors.initials: S
authors.lastname: Wen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fisch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000538:Aluminum Silicates / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077215:Clay; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010919:Placebos; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000538:Aluminum Silicates; D000972:Antineoplastic Agents, Phytogenic; D010919:Placebos; D000077146:Irinotecan; D000077215:Clay; D002166:Camptothecin