5-FU and CPT-11 significantly reduce intraperitoneal tumor growth in experimental investigations of peritoneal carcinomatosis
Arndt Hribaschek1, Frank Meyer1, Matthias Pross1, Karsten Ridwelski2, Regine Schneider-Stock3, Hans Lippert1; 1Department of Surgery, University Hospital, Magdeburg, Germany; 2Department of Surgery, Municipal Hospital, Magdeburg, Germany; 3Institute of Pathology, University Hospital, Magdeburg, Germany
After surgical resection of gastrointestinal cancer, recurrent tumor growth at the peritoneum remains an unsolved problem. Currently, there are no established or standardized protocols for the treatment or prevention of peritoneal carcinomatosis. The aim of the study was to investigate whether CPT-11 or 5-FU can decrease i.p. tumor growth and if there is a difference between both drugs. Methods: I.p. tumor growth was induced using a colon carcinoma cell line. The tumor cells were transferred into the abdominal cavity of WAG rats (weight 250-260 g). CPT-11 (group 1,2) and 5-FU (gr. 3,4) were administered i.p. (gr.1) and i.v. (gr.2) 10 min after tumor cell transfer (gr.A). In gr.B, an early postoperative chemotherapy was performed applying the drugs on d 5,10,15 after tumor cell transfer. After 30days, rats were sacrificed and tumor weight of the greater omentum and the mesenteric tissue was determined. In addition, characteristics of tumor growth such as frequency of histologically detectable tumor growth was assessed. Results: Table 1. In summary, both cytostatic dugs were able to significantly decrease the i.p. tumor weight after i.p. application. The greatest effect was achieved with direct intraoperative chemotherapy with slight differences between both drugs. In gr.B, the effect of both agents was also comparable. However, using the i.v. application route, neither CPT-11 nor 5-FU were capable to achieve a significant effect onto the i.p. tumor growth. In conclusion, 5-Fu and CPT-11 appear to be potential chemotherapeutic drugs providing a significant effect in the therapeutic management of peritoneal carcinomatosis under experimental conditions.
Characteristics of experimental tumor growth & the effects of i.p. versus i.v. chemotherapy.
| CATEGORY | Control I (NaCL, 0.9 % only) | Control II (Tumor cell transfer only) | A1(i.p.) Ox 300 mg/sqm | A2(i.v.) Ox 300 mg/sqm | A3(i.p.) 5-FU 425 mg/sqm | A4(i.v.) 5-FU 425 mg/sqm | B1(i.p.) Ox 300 mg/sqm | B2(i.v.) Ox 300 mg/sqm | B3(i.p.) 5-FU 425 mg/sqm | B4(i.v.) 5-FU 425 mg/sqm |
| Greater omentum [g] | 0.70+/-0.82 | 4.50+/-0.49 | 0.91+/-0.11 | 4.00+/-0.41 | 1.65+/-1.06 | 3.61+/-0.38 | 1.60+/-0.29 | 4.06+/-0.92 | 1.00+/-0.20 | 3.94+/-0.57 |
| Mesenteric tissue [g] | 1.94+/-0.11 | 5.18+/-0.51 | 2.68+/-0.25 | 4.98+/-0.63 | 2.47+/-0.63 | 5.25+/-0.70 | 2.74+/-0.11 | 4.97+/-0.29 | 2.45+/-0.25 | 4.88+/-1.36 |
| Histological tumor detection [n] | 0 | 8 | 6 | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
Ox, Oxaliplatin 5-FU, 5-Fluorouracil sqm, square meter
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