Androgen-dependent and
castration-resistant
prostate cancer (PC) is usually sensitive to
docetaxel chemotherapy. Nevertheless,
docetaxel resistance frequently appears after several cycles of treatment, raising the problem of
salvage treatment for
docetaxel-resistant PC patients. Although the combination of
docetaxel and
estramustine prolongs
metastasis-free and overall survival of patients with
androgen-independent PC, the use of this modality remains limited in elderly patients or patients with several comorbidities, especially
vascular disease or gastrointestinal toxicity, because of unacceptable toxicity including
venous thrombosis. The aims of this study were therefore (i) to evaluate the in-vivo efficacy of
estramustine combined with
docetaxel since initial
tumor growth and following the appearance of
docetaxel resistance in the
androgen-dependent human PC xenograft PAC120, and (ii) to evaluate the efficacy of
estramustine in six human
androgen-independent PC models derived from PAC120. In
docetaxel-resistant
tumor-bearing mice,
estramustine alone induced a TGD2 of 18 days, whereas the combination of
docetaxel and
estramustine induced a TGD2 of 50 days (P<0.05) with no significantly different overall survival of mice treated by
docetaxel and
estramustine since day 1 or since the onset of resistance to
docetaxel. Among the six human
androgen-independent
tumors treated with
estramustine alone, two highly sensitive models, two intermediate responding
tumors, and two resistant models were observed. Altogether, these results suggest that
estramustine should be combined with
docetaxel in PC patients, but the use of this treatment could be limited, particularly in elderly patients, to
docetaxel-resistant cases.