Treatment of Androgen-Independent Prostate Cancer Using Antimicrotubule Agents Docetaxel and Estramustine in Combination: An Experimental Study

Prostate. 2000 Sep 1;44(4):275-8. doi: 10.1002/1097-0045(20000901)44:4<275::aid-pros3>3.0.co;2-9.

Abstract

Background: Estramustine in combination with other chemotherapeutic agents has demonstrated synergy in hormone-refractory prostate cancer. Docetaxel has demonstrated antineoplastic activity in a variety of chemotherapeutic-unresponsive tumors. We evaluated the effects of estramustine and docetaxel in preclinical models of prostate cancer.

Methods: Cell viability of PC-3 and MAT-LyLu (MLL) cells were assessed 48 hr after drug treatment. For in vivo studies, each flank of five animals in six groups was injected with 1 x 10(6) MLL cells: control, estramustine, docetaxel (low- and high-dose), and low- and high-dose docetaxel with estramustine. Animals were treated on days 4 and 11, and sacrificed on day 14.

Results: The IC(50) value for docetaxel was 2 nM in the PC-3 cells and 40 nM in the MLL cells. The addition of 100 nM of estramustine did not alter the IC(50) value for PC-3 cells. In the MLL cells, however, the IC(50) value was lowered to 15 nM. In vivo, low-dose docetaxel with estramustine demonstrated antineoplastic activity similar to that of high-dose docetaxel alone, suggesting additive activity between the drugs.

Conclusions: These results demonstrate that when used in combination, docetaxel and estramustine can be more effective at lower dosages than when the individual drugs are used alone.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Estramustine / administration & dosage
  • Humans
  • Inhibitory Concentration 50
  • Male
  • Microtubules / drug effects
  • Neoplasm Transplantation
  • Neoplasms, Hormone-Dependent / drug therapy
  • Paclitaxel / administration & dosage
  • Paclitaxel / analogs & derivatives*
  • Prostatic Neoplasms / drug therapy*
  • Rats
  • Taxoids*
  • Tumor Cells, Cultured / drug effects

Substances

  • Taxoids
  • Docetaxel
  • Estramustine
  • Paclitaxel