Effectiveness of Oral Everolimus and Capecitabine Treatment on Peritoneal Carcinomatosis of Colorectal Origin
OP 196. Effectiveness of Oral Everolimus and Capecitabine Treatment on Peritoneal Carcinomatosis of Colorectal Origin
M. Eren Yuksel, O. Yuksel, E. Umit Bagriacik, O. Ekinci, T. Delibasi, S. Ozgermen, B. Ozgermen
Chair(s): Henrik Thorlacius, József Kaszaki & Mátyás Kiss
11:40 - 11:50h at Buda Room (B)
Categories: Gastrointestinal Surgery, Oral Session, Innovative Surgical Research, Novel Techniques and Product
Session: Oral Session XXI - Gastrointestinal Surgery II
Chair(s): Henrik Thorlacius, József Kaszaki & Mátyás Kiss
11:40 - 11:50h at Buda Room (B)
Categories: Gastrointestinal Surgery, Oral Session, Innovative Surgical Research, Novel Techniques and Product
Session: Oral Session XXI - Gastrointestinal Surgery II
Background
The mTOR inhibitor rapamycin has antitumor activity in colorectal cancer. Tumor suppression can further be enhanced when rapamycin is combined with intravenous 5-fluorouracil. Everolimus is a derivative of rapamycin with improved oral bioavailability. Capecitabine is as effective as intravenous 5-fluorouracil, and can be administered orally. The purpose of this study is to administer everolimus alone, and in conjunction with capecitabine in experimental nude mouse model to examine the effect on peritoneal carcinomatosis of colorectal origin.
The mTOR inhibitor rapamycin has antitumor activity in colorectal cancer. Tumor suppression can further be enhanced when rapamycin is combined with intravenous 5-fluorouracil. Everolimus is a derivative of rapamycin with improved oral bioavailability. Capecitabine is as effective as intravenous 5-fluorouracil, and can be administered orally. The purpose of this study is to administer everolimus alone, and in conjunction with capecitabine in experimental nude mouse model to examine the effect on peritoneal carcinomatosis of colorectal origin.
Materials and Methods
A model of peritoneal carcinomatosis of colorectal origin was established by transplanting Caco- 2 colon adenocarcinoma cells in BALB/cOlaHsd-Foxn1nu mice. Mice were randomized into four groups (everolimus, everolimus+capecitabine, capecitabine, and control), with two mice in each group. 7,5 mg/kg everolimus, and 2,1 mmol/kg capecitabine were orally administered. Excised tumors were weighed, and measured. Peritoneal lavage fluid, peritoneum, and intraabdominal organs were pathologically examined.
A model of peritoneal carcinomatosis of colorectal origin was established by transplanting Caco- 2 colon adenocarcinoma cells in BALB/cOlaHsd-Foxn1nu mice. Mice were randomized into four groups (everolimus, everolimus+capecitabine, capecitabine, and control), with two mice in each group. 7,5 mg/kg everolimus, and 2,1 mmol/kg capecitabine were orally administered. Excised tumors were weighed, and measured. Peritoneal lavage fluid, peritoneum, and intraabdominal organs were pathologically examined.
Results
Compared to control group, tumor size in mice receiving oral everolimus and/or capecitabine was approximately 20 times smaller. Comparing the tumor weight, there was no statistically significant difference within four groups (p=0.227). No malignant cells were detected in peritoneal lavage cytology. Despite the inhibiton of tumor growth, pathological examination revealed tumor cells in mesenteric and perisplenic lymph nodes. Liver examination revealed no toxicity.
Compared to control group, tumor size in mice receiving oral everolimus and/or capecitabine was approximately 20 times smaller. Comparing the tumor weight, there was no statistically significant difference within four groups (p=0.227). No malignant cells were detected in peritoneal lavage cytology. Despite the inhibiton of tumor growth, pathological examination revealed tumor cells in mesenteric and perisplenic lymph nodes. Liver examination revealed no toxicity.
Conclusion
The oral mTOR inhibitor everolimus alone, and in combination with capecitabine suppressed tumor growth in peritoneal carcinomatosis of colorectal origin. However, sample size should be increased in order to reach statistically significant data.
The oral mTOR inhibitor everolimus alone, and in combination with capecitabine suppressed tumor growth in peritoneal carcinomatosis of colorectal origin. However, sample size should be increased in order to reach statistically significant data.
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