High doses of taurolidine inhibit advanced intraperitoneal tumor growth in rats.
BACKGROUND
The antitumor agent taurolidine (TRD) affects tumor growth in animals. Thus far, no animal studies have been published concerning the systemic or local toxicity and the effectiveness of long-term intraperitoneal (i.p.) and intravenous (i.v.) administration on advanced tumor growths.


METHODS
In a first experiment (A) the systemic toxicity of the liver and kidneys was examined only after i.v. treatment in 40 rats (BD IX). For local toxicity the superior vena cava (SVC) was histologically analyzed. In a second study (B) 20,000 colon adenocarcinoma cells (DHD/K12/TRb) were initially applied i.p. after laparotomy in 80 rats (BD IX). After 28 days a port catheter system was placed in the SVC and left for 1 week. The animals were randomized into eight groups (n = 10) and received a 7-day treatment (eight hourly, 1 ml): 1, 2, 3% TRD or Ringer's solution (control group) either i.p. or i.v. Total i.p. tumor weight was measured 4 weeks after the end of the therapy. Side effects on differential blood counts and animal weight changes were examined.


RESULTS
No organ lesions were detected in liver, kidneys, and SVC in experiment A. The i.v. administration of 2% TRD (P = 0.034) and 3% TRD (P = 0.05) as well the i.p. application of 2% TRD (P = 0.05) decreased the development of advanced i.p. tumor lesions. No changes of differential blood count nor relevant animal weight changes resulted. Three port catheter-related infections were examined.


CONCLUSIONS
TRD does not impair the liver tissue, kidneys, SVC, and leucopoiesis. The intravenous therapy of 2% TRD is safe and anti-tumorigenic in advanced local tumor growth in rats.
Braumann
Chris
C
Department of General, Visceral, Vascular, and Thoracic Surgery, Humboldt University, Berlin, Germany. chris.braumann@charite.de
Stuhldreier
Benedikt
B
Bobrich
Eva
E
Menenakos
Charalambos
C
Rogalla
Stephan
S
Jacobi
Christoph A
CA
D000230:Adenocarcinoma; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000633:toxicity; D001706:Biopsy; D002455:Cell Division; D045744:Cell Line, Tumor; D056486:Chemical and Drug Induced Liver Injury; D003110:Colonic Neoplasms; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000473:pathology; D008297:Male; D009368:Neoplasm Transplantation; D010534:Peritoneal Neoplasms / Q000473:pathology* / Q000517:prevention & control*; D051381:Rats; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D013829:Thiadiazines / Q000008:administration & dosage* / Q000633:toxicity
D000970:Antineoplastic Agents; D013829:Thiadiazines; D013654:Taurine; C012566:taurolidine