Intraperitoneal versus intravenous CPT-11 given intra- and postoperatively for peritoneal carcinomatosis in a rat model.

Purpose: Peritoneal recurrence after resection of colorectal carcinoma is still a major concern. We investigated whether the novel cytostatic drug, CPT-11 (Irinotecan), delivered intraperitoneally (i.p.) and intravenously (i.v.), could inhibit intraperitoneal tumor spread in a rat model.

Methods: We induced intraperitoneal tumor growth using a tumor cell transfer model (10(6) cells) and divided the rats into the following five groups of eight: group IP1, given CPT-11 i.p. immediately after intraperitoneal tumor cell transfer; group IV1, given CPT-11 i.v. immediately after intraperitoneal tumor cell transfer; group IP2, given CPT-11 i.p. on postoperative days (PODs) 5, 10, and 15; group IV2, given CPT-11 on PODs 5, 10, and 15; and a control group. The rats were killed 30 days after tumor cell transfer, and the tumor weight, number of nodes in the greater omentum and peritoneum, presence of metastases in the liver and lungs, and ascites volume were determined.

Results: CPT-11 inhibited peritoneal tumor growth significantly. The direct intraoperative intraperitoneal application induced a more pronounced effect than the early postoperative intraperitoneal application, but both these application modes were superior to the intravenous route, which had no significant effect.

Conclusion: CPT-11 was highly efficacious against peritoneal carcinomatosis in this experimental model. The combination of CPT-11 with other cytostatic agents and drugs generating different effector mechanisms may diminish or even prevent intraperitoneal tumor growth.