Inhibition of growth of experimental prostate cancer with sustained delivery systems (microcapsules and microgranules) of the luteinizing hormone-releasing hormone antagonist SB-75

E. Korkut, L. Bokser, A. M. Comaru-Schally, K. Groot, A. V. Schally

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Inhibitory effects of the sustained delivery systems (microcapsules and microgranules) of a potent antagonist of luteinizing hormone-releasing hormone N-Ac-[3-(2-naphthyl)-D-alanine1, 4-chloro-D-phenylalanine2, 3-(3-pyridyl)-D-alanine3, D-citrulline6, D-alanine10]LH-RH (SB-75) on the growth of experimental prostate cancers were investigated. In the first experiment, three doses of a microcapsule preparation releasing 23.8, 47.6, and 71.4 μg of antagonist SB-75 per day were compared with microcapsules of agonist [D-Trp6]LH-RH liberating 25 μg/day in rats bearing Dunning R3327H transplantante prostate carcinoma. During 8 weeks of treatment, tumor growth was decreased by [D-Trp6]LH-RH and all three doses of SB-75 as compared to untreated controls. The highest dose of SB-75 (71.4 μg/day) caused a greater inhibition of prostate cancer growth than [D-Trp6]LH-RH as based on measurement of tumor volume and percentage change hi tumor volume. Doses of 23.8 and 47.6 μg of SB-75 per day induced a partial and submaximal decrease, respectively, in tumor weight and volume. Tumor doubling time was the longest (50 days) with the high dose of SB-75 vs. 15 days for controls. The body weights were unchanged. The weights of testes, seminal vesicles, and ventral prostate were greatly reduced in all three groups that received SB-75, and testosterone levels were decreased to nondetectable values in the case of the two higher doses of SB-75. LH levels were also diminished. Similar results were obtained in the second experiment, in which the animals were treated for a period of 8 weeks with microgranules of SB-75. Therapy with microgranules of SB-75 significantly decreased tumor growth as measured by the final tumor volume, the percentage change from the initial tumor volume, and the reduction in tumor weight. The results indicate that antagonist SB-75, released from sustained delivery systems, can produce a state of chemical castration and effectively inhibit the growth of experimental prostate cancers. The efficacy of the antagonist SB-75 in inhibiting androgen-dependent Dunning prostatic carcinoma and the absence of side effects suggest its possible usefulness for the treatment of hormone-sensitive tumors. (.

Original languageEnglish (US)
Pages (from-to)844-848
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number3
DOIs
StatePublished - 1991

Keywords

  • Chemical castration
  • Hormone-sensitive cancers
  • Luteinizing hormone-releasing hormone analogs

ASJC Scopus subject areas

  • General
  • Genetics

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