title: Intestinal permeability in patients with metastatic colon cancer treated with patupilone.
abstract: BACKGROUND
  Only a limited number of cytotoxic drugs have shown activity in metastatic colorectal carcinoma. Patupilone is a novel agent with promising activity in this common cancer. Diarrhea represents the dose-limiting toxicity of patupilone. Measurement of intestinal permeability is one of the potential methods of non-invasive laboratory assessment of gastrointestinal toxicity.
  
  
  METHODS
  We have assessed intestinal permeability by measuring absorption of lactulose, mannitol and xylose in 27 previously treated patients with metastatic colorectal cancer enrolled in a phase I trial of patupilone.
  
  
  RESULTS
  Lactulose/mannitol and lactulose/xylose ratios increased after the treatment. Significantly higher lactulose/mannitol ratio was observed in patients who had severe diarrhea. Moreover, patients who subsequently had an adverse event of grade 3 or higher had significantly higher baseline lactulose/mannitol or lactulose/xylose ratios.
  
  
  CONCLUSIONS
  Measurement of intestinal permeability using the lactulose/mannitol test may represent a biomarker for the monitoring, or even prediction of toxicity of cytotoxic drugs, including patupilone.
authors.forename: Bohuslav
authors.initials: B
authors.lastname: Melichar
authors.forename: Radomír
authors.initials: R
authors.lastname: Hyšpler
authors.forename: Alena
authors.initials: A
authors.lastname: Tichá
authors.forename: Hana
authors.initials: H
authors.lastname: Kalábová
authors.forename: Denisa
authors.initials: D
authors.lastname: Vitásková
authors.forename: Michaela
authors.initials: M
authors.lastname: Zezulová
authors.forename: Josef
authors.initials: J
authors.lastname: Dvořák
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Cerman
authors.forename: Martin
authors.initials: M
authors.lastname: Doležel
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003967:Diarrhea / Q000209:etiology; D034261:Epothilones / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D007792:Lactulose / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary; D008297:Male; D008353:Mannitol / Q000378:metabolism; D008875:Middle Aged; D010539:Permeability / Q000187:drug effects; D014994:Xylose / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; D008353:Mannitol; D007792:Lactulose; D014994:Xylose; C093788:epothilone B