Influence of various aministration routes on the antitumor efficacy of TT-232, a novel somatostatin analog

M. Tejeda, D. Gaal, R. E. Schwab, A. Pap, T. Szúts, Gy Keri

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

TT-232 a novel tumor-selective somatostatin analog with a five residue ring structure (D-Phe-Cys-Tyr-D-Trp-Lys-Cys-Thr-NH2) was developed by us and published in an earlier work. This synthetic heptapeptide had no effect on growth hormone release, but had a remarkable tyrosine-kinase inhibitory effect and inducted apoptosis. The aim of this study was to term administration routes and treatment schedules. The effectiveness of TT-232 was studied on different rodent tumors transplanted to inbred mice from SPF breeding. Intermittent treatment by injections and continuous infusion of TT-232 using a s.c., i.p. or i.v. implanted Alzet type osmotic minipump were compared for therapeutic efficacy. The treatments were started either on the day subsequent to tumor transplantation or after the development of a tumor. On the basis of survival and tumor growth inhibition the infusion of TT-232 for 14 days using an implantable osmotic pump proved to be a much more effective route of treatment in both s.c. and i.v. administration than the intermittent injections applied twice a day for 2 weeks. In the case of S-180 sarcoma the continuous administration of TT-232 for 14 days using s.c. implanted osmotic pump resulted in 60% the i.v. infusion produced 40% long-term (over 80 days) and tumor free survivors. By the continuous administration of TT-232, an 80-100% tumor growth inhibitory effect and a considerable retardation of tumor development could be achieved. Continuous infusion from implanted pumps ensured a constant drug level and resulted in a well-defined, consistent pattern of drug exposure over the full duration of drug administration. In our study the route of infusion has been shown to increase drug efficacy relative to conventional delivery methods.

Original languageEnglish
Pages (from-to)1023-1027
Number of pages5
JournalAnticancer research
Volume20
Issue number2 A
Publication statusPublished - May 16 2000

Keywords

  • Alzet osmotic minipump
  • Continuous drug delivery
  • New somatostatin analog
  • TT-232
  • Tumor therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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