title: Prevention of irinotecan induced diarrhea by probiotics: A randomized double blind, placebo controlled pilot study.
abstract: OBJECTIVE
  Diarrhea is one of the dose limiting toxicity of irinotecan. SN-38 is main irinotecan metabolite responsible for diarrhea development, which is excreted in glucuronidated form into the intestine. This study aimed to determine the effectiveness of the probiotics in the prevention of irinotecan induced diarrhea due to reduction of intestinal beta-d-glucuronidase activity.
  
  
  METHODS
  Between January 2011 and December 2013, 46 patients with colorectal cancer starting a new line of irinotecan based therapy were included. Patients were randomized 1:1 to probiotics (PRO) or placebo (PLA). Probiotic formula Colon Dophilus™, was administered at a dose of 10×10(9)CFU of bacteria tid, orally for 12 weeks of chemotherapy. The study was prematurely terminated due to slow accrual, when 46 of 220 planned patients were accrued.
  
  
  RESULTS
  Twenty-three patients were randomized to PRO and 23 patients to PLA. Administration of probiotics compared to placebo led to a reduction in the incidence of severe diarrhea of grade 3 or 4 (0% for PRO vs. 17.4% for PLA, p=0.11), as well as reduction of the overall incidence of diarrhea (39.1% for PRO vs. 60.9% for PLA, p=0.24) and incidence of enterocolitis (0% for PRO vs. 8.7% for PLA). Patients on PRO used less antidiarrheal drugs compared to PLA. There was no infection caused by probiotic strains recorded.
  
  
  CONCLUSIONS
  Administration of probiotics in patients with colorectal cancer treated with irinotecan-based chemotherapy is safe and could lead to a reduction in the incidence and severity of gastrointestinal toxicity.
authors.affiliation: 2nd Department of Oncology and National Cancer Institute, Comenius University, Faculty of Medicine, Klenova 1, 833 10 Bratislava, Slovakia. Electronic address: misomego@gmail.com.
authors.forename: Michal
authors.initials: M
authors.lastname: Mego
authors.affiliation: Department of Oncology, St. Jacob Hospital, Bardejov, Slovakia.
authors.forename: Jozef
authors.initials: J
authors.lastname: Chovanec
authors.affiliation: 2nd Department of Oncology and National Cancer Institute, Comenius University, Faculty of Medicine, Klenova 1, 833 10 Bratislava, Slovakia.
authors.forename: Iveta
authors.initials: I
authors.lastname: Vochyanova-Andrezalova
authors.affiliation: Regional Cancer Center, Komarno, Slovakia.
authors.forename: Peter
authors.initials: P
authors.lastname: Konkolovsky
authors.affiliation: St. Elisabeth Cancer Institute, Bratislava, Slovakia.
authors.forename: Milada
authors.initials: M
authors.lastname: Mikulova
authors.affiliation: Regional Cancer Center, Poprad, Slovakia.
authors.forename: Maria
authors.initials: M
authors.lastname: Reckova
authors.affiliation: 1st Department of Oncology and St. Elisabeth Cancer Institute, Comenius University, Faculty of Medicine, Bratislava, Slovakia.
authors.forename: Vera
authors.initials: V
authors.lastname: Miskovska
authors.affiliation: Department of Oncology, Trencin Hospital, Trencin, Slovakia.
authors.forename: Branislav
authors.initials: B
authors.lastname: Bystricky
authors.affiliation: Regional Cancer Center, Poprad, Slovakia.
authors.forename: Juraj
authors.initials: J
authors.lastname: Beniak
authors.affiliation: Regional Cancer Center, Poprad, Slovakia.
authors.forename: Lenka
authors.initials: L
authors.lastname: Medvecova
authors.affiliation: Pharmaceutical Faculty, Comenius University, Bratislava, Slovakia.
authors.forename: Adela
authors.initials: A
authors.lastname: Lagin
authors.affiliation: 2nd Department of Oncology and National Cancer Institute, Comenius University, Faculty of Medicine, Klenova 1, 833 10 Bratislava, Slovakia.
authors.forename: Daniela
authors.initials: D
authors.lastname: Svetlovska
authors.affiliation: 1st Department of Oncology and St. Elisabeth Cancer Institute, Comenius University, Faculty of Medicine, Bratislava, Slovakia.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Spanik
authors.affiliation: Cancer Research Institute, Bratislava, Slovakia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Zajac
authors.affiliation: 2nd Department of Oncology and National Cancer Institute, Comenius University, Faculty of Medicine, Klenova 1, 833 10 Bratislava, Slovakia.
authors.forename: Jozef
authors.initials: J
authors.lastname: Mardiak
authors.affiliation: 2nd Department of Oncology and National Cancer Institute, Comenius University, Faculty of Medicine, Klenova 1, 833 10 Bratislava, Slovakia.
authors.forename: Lubos
authors.initials: L
authors.lastname: Drgona
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives*; D003967:Diarrhea / Q000139:chemically induced* / Q000188:drug therapy / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019936:Probiotics / Q000627:therapeutic use*
chemical_list: D000077146:Irinotecan; D002166:Camptothecin
keywords: Diarrhea; Irinotecan; Prevention; Probiotics