Influence of various administration routes on the antitumor activity of a somatostatin analog, TT-232

M.Tejeda1, D. Gaál 1, Gy Kéri 2

1 National Institute of Oncology, Budapest, Hungary. 2 Institute of Biochemistry, Semmelweis Uni.Med.Sch.,Budapest,Hungary.

AIM: the aim of our study to compare the therapeutic effectiveness of TT-232 applying it in various long-term administration routes and treatment-schedules. METHODS: the antiproliferative effect of TT-232 was investigated on different transplantable rodent tumors (S-180 sarcoma, Coplon-26 carcinoma, P-388 lymphoid leukemia, MXT mammary carcinoma) and human cancer xenograft (MDA-MB-231 breast carcinoma, PC-3 prostate tumor). Intermittent treatment by s.c., i.p. or i.v. injections and that of the continuous infusion of TT-232 using s.c. or i.v. implanted Alzet type osmotic minipump were compared for therapeutic efficacy. The antitumor activity of TT-232 was evaluated on the basis of survival and tumor growth inhibition. RESULTS: the continuous infusion proved to be a much more effective route of treatment in all type of administration than the intermittent injections applied twice a day for 2 weeks. In the case of S-180 sarcoma the infusion using s.c. implanted minipump resulted in 60%, the i.v. infusion produced 40% long-term and tumor-free survival of TT-232 treated mice. During TT-232 infusion 80-100% tumor growth inhibitory effect and a considerable retardation of tumor development were achieved. CONCLUSION: infusion from implanted osmotic minipump maintaining constant drug level and resulting in a well-defined, consistent pattern of drug exposure throughout the period of drug administration suggests the potential benefits of TT-232 in clinical practice.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Novel Therapies, Part 1.