title: Gastrointestinal permeability in ovarian cancer and breast cancer patients treated with paclitaxel and platinum.
abstract: BACKGROUND
  Combination of platinum derivatives with paclitaxel is currently the standard front line regimen for patients with epithelial ovarian carcinoma, and represents also an active regimen in patients with metastatic breast or unknown primary carcinomas. Measurement of intestinal permeability represents one of the potential methods of noninvasive laboratory assessment of gastrointestinal mucositis induced by chemotherapy, but little is known about intestinal permeability in patients treated with paclitaxel or platinum.
  
  
  METHODS
  Intestinal permeability was assessed in 36 breast and ovarian cancer patients treated with paclitaxel/platinum combination by measuring, using capillary gas chromatography, urinary sucrose, lactulose, xylose and mannitol after oral challenge. The significance of differences during the therapy compared to pre-treatment values was studied by Wilcoxon paired test. The differences between groups of patient were studied by Mann-Whitney U test. Fisher exact test was used to compare the frequency in different subgroups.
  
  
  RESULTS
  After administration of the first dose, a significant (p < 0.05) decrease in xylose absorption and increased lactulose/mannitol, sucrose/mannitol, lactulose/xylose and sucrose/xylose ratios were observed, but these parameters returned subsequently to pre-treatment levels. Patients who experienced serious (grade 3 or 4) toxicity had at baseline significantly lower percentages of xylose, mannitol and sucrose, and higher lactulose/mannitol ratio. Nine of 13 (69%) patients with baseline lactulose/mannitol ratio 0.070 or above experienced serious toxicity compared to 4 out of 23 patients (17%) with the ratio below 0.070 (p = 0.002). Post-treatment lactulose, lactulose/mannitol, sucrose/mannitol and lactulose/xylose ratios were significantly increased in patients with serious toxicity.
  
  
  CONCLUSIONS
  A transient significant increase in lactulose/monosaccharide and sucrose/monosaccharide ratios was observed in ovarian and breast cancer patients treated with paclitaxel and platinum. Increased lactulose absorption, lactulose/mannitol, sucrose/mannitol and lactulose/xylose ratios were evident in patients with grade 3 or 4 toxicity, and increased baseline lactulose/mannitol ratio predicted serious toxicity.
authors: Department of Oncology & Radiotherapy, Charles University Medical School & Teaching Hospital, Sokolská 581, Building 23, 500 05, Hradec Králové, Czech Republic. melichar@fnhk.cz
authors: Bohuslav
authors: B
authors: Melichar
authors: Radomír
authors: R
authors: Hyspler
authors: Emanuela
authors: E
authors: Dragounová
authors: Josef
authors: J
authors: Dvorák
authors: Hana
authors: H
authors: Kalábová
authors: Alena
authors: A
authors: Tichá
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D007792:Lactulose / Q000378:metabolism; D008353:Mannitol / Q000378:metabolism; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D013395:Sucrose / Q000378:metabolism; D000068878:Trastuzumab; D014994:Xylose / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008353:Mannitol; D007792:Lactulose; D013395:Sucrose; D014994:Xylose; D016190:Carboplatin; D000068878:Trastuzumab; D017239:Paclitaxel; D002945:Cisplatin
references: Cancer Treat Rep. 1982 Jun;66(6):1435-6
references: 7083246
references: Cancer. 2004 May 1;100(9 Suppl):2026-46
references: 15108223
references: BMJ. 1990 Jan 27;300(6719):230-5
references: 2106931
references: Gastroenterology. 1993 Jun;104(6):1619-26
references: 8500718
references: Gastroenterology. 1995 May;108(5):1566-81
references: 7729650
references: N Engl J Med. 1996 Jan 4;334(1):1-6
references: 7494563
references: J Clin Oncol. 1997 Jun;15(6):2254-61
references: 9196138
references: J Clin Oncol. 1997 Jun;15(6):2385-93
references: 9196154
references: Scand J Gastroenterol Suppl. 1997;223:70-8
references: 9200310
references: Nutrition. 1999 Jul-Aug;15(7-8):546-9
references: 10422084
references: J Natl Cancer Inst. 2004 Nov 17;96(22):1682-91
references: 15547181
references: Ann Oncol. 2005 May;16(5):749-55
references: 15817604
references: Chemotherapy. 2005 Oct;51(6):336-8
references: 16224185
references: Ann Oncol. 2004 Oct;15(10):1517-26
references: 15367413
references: J Natl Cancer Inst. 2000 May 3;92(9):699-708
references: 10793106
references: J Clin Gastroenterol. 2001 Mar;32(3):228-30
references: 11246350
references: J Cancer Res Clin Oncol. 2001 May;127(5):314-8
references: 11355146
references: J Clin Gastroenterol. 2002 Apr;34(4):385-96
references: 11907349
references: Cancer Chemother Pharmacol. 2002 Apr;49(4):294-8
references: 11914908
references: Gynecol Oncol. 2003 Jan;88(1):51-7
references: 12504627
references: Ann Oncol. 2003 Jul;14(7):1086-93
references: 12853351
references: Support Care Cancer. 2004 Apr;12(4):227-33
references: 14752625
references: Cancer. 2004 May 1;100(9 Suppl):1995-2025
references: 15108222
references: Cancer Res. 1989 Jul 1;49(13):3689-91
references: 2731182