Gastrointestinal permeability in ovarian cancer and breast cancer patients treated with paclitaxel and platinum.
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.
Melichar
Bohuslav
B
Department of Oncology & Radiotherapy, Charles University Medical School & Teaching Hospital, Sokolská 581, Building 23, 500 05, Hradec Králové, Czech Republic. melichar@fnhk.cz
Hyspler
Radomír
R
Dragounová
Emanuela
E
Dvorák
Josef
J
Kalábová
Hana
H
Tichá
Alena
A
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
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008353:Mannitol; D007792:Lactulose; D013395:Sucrose; D014994:Xylose; D016190:Carboplatin; D000068878:Trastuzumab; D017239:Paclitaxel; D002945:Cisplatin
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