Fünf Chemotherapeutika in tierexperimentellen Untersuchungen zur Prävention und Therapie der Peritonealkarzinose

 

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Zusammenfassung

Nach chirurgischer Resektion von soliden gastrointestinalen Tumoren (Magen-, Pankreas-, kolorektales Karzinom) stellen hohe lokale Rezidivraten im ehemaligen Tumorbett oder am Peritoneum ein noch immer ungelöstes Problem dar. So existieren zurzeit keine standardisierten Therapieprotokolle zur Prophylaxe oder Behandlung der Peritonealkarzinose.
In einem tierexperimentellen Modell an der Ratte wurden die fünf Chemotherapeutika Mitomycin, Cisplatin, 5-FU, Oxaliplatin und CPT-11 (je Chemotherapeutikum n = 24) hinsichtlich eines möglichen präventiven oder therapeutischen Potenzials bei Peritonealkarzinose nach intraperitonealer (i. p.) Applikation untersucht. Die Untersuchungen wurden in drei Gruppen (je Gruppe n = 8) mit zwei zusätzlichen Kontrollgruppen vorgenommen. In der ersten Gruppe wurden die Zytostatika direkt nach Tumorzellimplantation in die Peritonealhöhle appliziert. Eine frühe postoperative i. p. Chemotherapie (d 5, 15, 20) wurde in der zweiten Gruppe verabreicht. In der dritten Gruppe wurde ein späte i. p. Chemotherapie (d 15, 20, 25) über ein implantiertes Portsystem unter der Intention gegeben, eine bereits bestehende Peritonealkarzinose zu beeinflussen.
Die Ergebnisse zeigten, dass nach direkter intraoperativer i. p. Chemotherapie Mitomycin und Cisplatin hocheffektiv waren, ein i. p. Tumorwachstum zu vermeiden. Nach früher postoperativer, d. h. intermittierender i. p. Chemotherapie konnten die Zytostatika 5-FU und CPT-11 das i. p. Tumorwachstum am effektivsten reduzieren. Im Gegensatz dazu konnte keine der verwendeten Substanzen eine bereits manifestierte Peritonealkarzinose signifikant beeinflussen.
Die Daten sprechen dafür, dass neuere Substanzen hinsichtlich ihres Potenzials zur Beeinflussung des i. p. Tumorwachstums überprüft werden sollten. Dabei sollte ein Vergleich mit den etablierten Substanzen vorgenommen werden.

Abstract

High local recurrence rates within the previous tumor bed or at the peritoneum remain an unsolved problem after surgical resection of malignant gastrointestinal tumors such as gastric, colorectal or pancreatic carcinoma. Currently, there are no standardized treatment protocols available for the prevention or treatment of peritoneal carcinomatosis. In a basic experimental trial, mitomycin, cisplatin, 5-FU, oxaliplatin and CPT-11 were used to prevent or treat peritoneal carcinomatosis induced in rats.
Experiments were performed in three groups (n = 8 each) of animals plus two control groups. In the first 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 second group, early postoperative intraperitoneal (i. p.) chemotherapy (day [d] 5, 10, 15 following surgical intervention for tumor cell transfer) was administered, whereas in the third group, late i. p. chemotherapy (d 15, 20, 25 following surgery) was given via a port-a-cath aiming for significant reduction of a visible, already established peritoneal carcinomatosis. Mitomycin and cisplatin were highly effective to prevent peritoneal carcinomatosis (direct application immediately after tumor cell transfer - 1^st treatment group). Using early postoperative i. p. chemotherapy (2^nd group), 5-FU and CPT-11 were shown to be significantly effective to reduce the intraperitoneal tumor spread. None of the cytostatic agents was able to decrease significantly an already generated peritoneal carcinomatosis (3^rd treatment group).
The results suggest that novel chemotherapeutic drugs should be proven for their potential to alter peritoneal metastases of GI tumors i) in comparison with established drugs and ii) depending on the application time and mode.

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Dr. med. A. Hribaschek

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