High local recurrence rates within the previous tumor bed or at the peritoneal site remain an unsolved problem after resection of malignant GI tumor lesions such as gastric, colorectal or pancreatic carcinoma(Ca). Currently, there are no standardized treatment protocols available for the prevention or treatment of peritoneal carcinomatosis.The aim of this systematic comparative study was to investigate whether various cytostatic substances tested previously in single studies on the application mode are able to prevent or treat experimentally induced peritoneal carcinomatosis in rats.
Methods: In a basic experimental trial, established and novel antineoplastic drugs such as mitomycin, cisplatin, 5-FU, oxaliplatin and CPT-11 (limited dosage adapted according to their LD50) were used to prevent or treat peritoneal carcinomatosis induced in rats by transfer of 1,000,000 tumor cells (colon adenocarcinoma cell line CC-531; Cell-Lines Service, Heidelberg, Germany) via laparotomy. Experiments were performed in 3 groups (n=8 each) of animals depending of the application time of drugs after tumor sell transfer plus 2 control groups (sham operation -/+ saline).
Results: In the 1st group, Mitomycin, Cisplatin, 5-FU, Oxaliplatin and CPT-11 (n=24 each) were applied directly following tumor cell implantation into the peritoneal cavity. In the 2nd group, early postoperative intraperitoneal (i.p.) chemotherapy (day[d] 5,10,15 following tumor cell transfer, i.e., 3 separate dosages) was administered whereas in the 3rd group, late i.p. chemotherapy (d15,20,25 following surgery) was given via a previously implantated port-a-cath aiming for significant reduction of a visible, already established peritoneal carcinomatosis. Mitomycin and cisplatin were highly effective to prevent peritoneal carcinomatosis versus controls (direct application immediately after tumor cell transfer - 1st treatment group). Using early postoperative i.p. chemotherapy (2nd group), 5-FU and CPT-11 were shown to be significantly effective to reduce the i.p. tumor spread versus controls. None of the cytostatic agents was able to decrease significantly an already manifest peritoneal carcinomatosis (3rd treatment group).
Conclusion: The results suggest that novel chemotherapeutic drugs or their combination should be further proven in a systematic experimental setting for their potential to significantly alter peritoneal metastases of GI tumors i) in comparison with established drugs and ii) depending on the application time and mode (e.g., i.p. versus i.v.) but also iii) with regard to their effect on wound and anastomosis healing as well as induction of peritonitis or further side effects.