Response to second-line taxane-based therapy after first-line epothilone B analogue BMS-247550 (BMS) therapy in hormone refractory prostate cancer (HRPC)

Abstract

4564 Background: Epothilone analogues and taxanes exert anti-cancer activity by interfering with microtubule function. BMS is an epothilone analogue that has activity in taxane-resistant cell lines and as first-line therapy in HRPC patients (pts). Clinical cross resistance of BMS with taxanes is not known. The utility of second-line taxane therapy was evaluated in a cohort of HRPC pts previously treated with BMS. Methods: Records from HRPC pts treated on a randomized phase II trial of BMS with or without estramustine (E) and who received taxane-based second-line therapy were evaluated. PSA response and time to PSA progression (TTPP) were defined by Consensus Criteria. Results: 29 pts received BMS with (18) or without (11) E and subsequent second-line taxane therapy. Second-line therapy consisted of E/docetaxel (D) (19), single agent D (3), E/paclitaxel (P)/carboplatin (3), E/P (2), D/calcitriol (1), or D/cyclophosphamide (1). The overall PSA response to second-line therapy was 59% (95% CI= 39–77%). Median TTPP for pts treated with a second-line taxane was 4.9 months. No difference in response to second-line taxane therapy was seen in pts based on whether or not they received first-line E therapy. The PSA response proportion to second-line taxane therapy in pts who had obtained a PSA response to front-line BMS was 68% (95% CI= 43–87%), compared with 40% (95% CI= 12–74%) for pts who did not have a PSA response to BMS (p= 0.23). The median TTPP on second-line taxane therapy in pts who had obtained a PSA response to front-line BMS was 5.7 months, compared with 1.4 months for pts who did not have a PSA response to BMS (p= 0.19). Conclusions: Second-line taxane therapy following BMS results in a PSA response proportion of 59%. Response to second-line taxane therapy does not appear conditional on response to first-line BMS therapy. Second-line PSA responses are independent of prior E treatment, suggesting that these response frequencies are not simply due to treatment of E-naïve pts with E. A trial of second-line BMS following progression on taxane-based first-line therapy is underway. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis