Treatment of androgen-independent prostate cancer using antimicrotubule agents docetaxel and estramustine in combination: an experimental study

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 × 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.

Treatment of androgen-independent, hormone-refractory prostate cancer with docetaxel in Japanese patients

“…Docetaxel inhibits tumor growth by the induction of microtubule stabilization and the promotion of bcl-2 inactivation, which effects induce apoptosis. 9,10 Docetaxel has an obvious anti-tumor effect on prostate cancer cells, 11,12 and it has been used clinically in HRPC patients. In 1999, Picus and Schultz 13 demonstrated that 75 mg/m 2 docetaxel treatment every 3 weeks had a significant effect in HRPC patients.…”

Advances in Prostate Cancer Chemotherapy: A New Era Begins

“…The most active agent preclinically and clinically was docetaxel, either alone or in combination with estramustine. [28][29][30] Docetaxel, a semisynthetic taxane, likely has multiple mechanisms of antineoplastic activity. Microtubule stabilization, the most widely accepted mechanism of action, involves binding of docetaxel to ␤-tubulin, thus promoting polymerization (Figure 3).…”

Poly(styrene)-b-poly(DL-lactide) copolymer-based nanoparticles for anticancer drug delivery

“…32,33 DCT concentration (1-100 nM) in this study was set up considering its reported IC 50 values in PC-3 cells. [34][35][36] Cell viability was measured using an MTS-based assay after 48 and 72 hours of incubation of Taxotere and PS-PDLLA/ DCT NPs. At all DCT concentration (1, 10 and 100 nM) and incubation time (48 and 72 hours) groups, the cell viability (%) of the PS-PDLLA/DCT NP-treated group was lower than that of the Taxotere group (P0.05).…”