Does the administration route of leucovorin have any influence on the impairment of colonic healing caused by intraperitoneal 5-fluorouracil treatment?

Intraperitoneal chemotherapy with li-fluorouracil (5-FU) is a new, promisin g alternative in adjuvant treatment of advanced colorectal cancer. Leucovor in (LV), a biomodulator of 5-FU, potentiates the antineoplastic effect of 5 -FU. The aim of this study was to determine whether the administration rout es of LV had any influence on the impairment of colonic healing caused by i ntraperitoneal 5-FU treatment. 48 male Wistar rats were subjected to left c olonic resection and anastomosis, and randomized to 1 of 4 groups: control group (receiving intraperitoneal NaCl, intravenous NaCl); ipFU group (recei ving intraperitoneal 5-FU, intravenous NaCl); ipFU+ivLV group (receiving in traperitoneal 5-FU, intravenous LV), and ipFU+LV group (receiving intraperi toneal 5-FU+LV, intravenous NaCl). Treatment was started after surgery and continued for 5 days with daily injections. The animals were sacrificed on the 7th day postoperatively. Anastomotic complications were more common in the ipFU, ipFU+ivLV, and ipFU+LV groups (p < 0.05) compared to the control group. The anastomotic breaking strength was significantly reduced in the i pFU, ipFU+ivLV, ipFU+LV groups (p < 0.05) than in the control group, but it did not differ between the ipFU, ipFU+ivLV, and ipFU+LV groups. The hydrox yproline content of the anastomotic segment was also significantly reduced in the ipFU, ipFU+ivLV and ipFU+LV groups (p < 0.05) compared to the contro l group. However, there was no difference between the anastomotic hydroxypr oline content of the ipFU, ipFU+ivLV, and ipFU+LV groups. In this experimen t, colonic healing was impaired after intraperitoneal 5-FU administration a s judged by the higher rates of anastomotic complications, reductions in an astomotic breaking strength and hydroxyproline content; but LV administrati on either intravenously or intraperitoneally did not cause further deterior ation in colonic healing. Copyright (C) 2001 S. Karger AG, Baser.