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Inhibition of prostate cancer growth by 9-aminocamptothecin and estramustine

H Naik1, J E Lehr, K J Pienta

  • 1Michigan Prostate Institute, University of Michigan Comprehensive Cancer Center, University of Michigan School of Medicine, Ann Arbor 48109-0680, USA.

Urology
|September 1, 1996
PubMed
Abstract

Insights

Combining estramustine and 9-aminocamptothecin (9-AC) shows significant preclinical activity against hormone-refractory prostate cancer. This combination therapy is more cytotoxic than single agents, prompting clinical trials.

Area of Science:

  • Oncology
  • Pharmacology
  • Cancer Biology

Background:

  • Hormone-refractory prostate cancer (HRPC) has a poor prognosis.
  • Nuclear matrix-targeting agents show promise in HRPC treatment.
  • Estramustine and 9-aminocamptothecin (9-AC) are agents with potential activity.

Purpose of the Study:

  • To evaluate the efficacy of estramustine and 9-AC in a preclinical HRPC model.
  • To assess the combined effect of estramustine and 9-AC on prostate cancer cell growth.
  • To investigate the mechanism of action at the nuclear matrix level.

Main Methods:

  • Utilized the Dunning rat prostatic adenocarcinoma model.
  • Investigated the interaction of estramustine and 9-AC with the nuclear matrix.
  • Assessed cytotoxicity in vitro and in vivo in rat models.

Main Results:

  • The combination of estramustine and 9-AC demonstrated significant cytotoxicity against rat and human prostate cancer cells.
  • Pharmacologically achievable doses of the combination were effective.
  • The combined treatment was more cytotoxic than either agent alone.

Conclusions:

  • Estramustine and 9-AC combination therapy is a promising strategy for HRPC.
  • Preclinical findings support the initiation of a Phase II clinical trial for HRPC patients.
  • Further clinical investigation of 9-AC-based regimens is warranted.

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