Abstract
4623 Background: Estramustine in combination with taxanes has demonstrated synergistic antitumor activity in patients (pts) with hormone-refractory prostate cancer. However, taxanes are associated with hematologic toxicity and the development of drug resistance. EPO906 is a novel epothilone that induces microtubule polymerization and has demonstrated clinical cytotoxic activity in taxane-sensitive, -resistant, and -refractory tumors. Phase I studies show EPO906 has a favorable safety profile compared with docetaxel. Methods: We investigated the MTD of EPO906 plus estramustine in pts with advanced cancer. Pts with stage III/IV solid tumors and a performance status ≤ 2 were eligible. DLT was defined as grade (gr) 4 neutropenia and thrombocytopenia, febrile neutropenia, ≥ gr 3 nonhematologic toxicity, or gr 2 renal toxicity. Pts received weekly oral estramustine 280 mg BID days 1 - 3 and EPO906 starting at 0.5 mg/m2 via 5-min IV infusion weekly on day 2 for 3 wk followed by 1 wk of rest. EPO906 was escalated by 0.5-mg/m2 increments to 2.5 mg/m2 in cohorts of 3 - 6 pts. Results: Thus far, 14 pts have been enrolled. Tumor types are predominantly prostate and breast cancer. All pts except 1 had received prior taxane therapy. Median age was 61 yrs (range, 40 - 75 yrs). Three pts were treated in cohort 1 (0.5 mg/m2), 3 in cohort 2 (1.5 mg/m2), 4 in cohort 3 (2.0 mg/m2), and 4 in cohort 4 (2.5 mg/m2). One pt in cohort 3 experienced a DLT (gr 3 diarrhea). Eight pts experienced gr 3 and 1 pt experienced gr 4 adverse events, including fatigue, vomiting, and diarrhea. The most frequent gr 1 and 2 toxicities were diarrhea and nausea (most likely associated with estramustine). One pt experienced gr 3 anemia; no other pts had severe hematologic toxicity. Preliminary tumor assessment showed 1 pt with PR and 8 pts with SD (3 for 4 months; 5 for 2 months). The MTD of EPO906 in combination with estramustine is 2.5 mg/m2. Conclusion: Preliminary results suggest that EPO906 plus estramustine is generally well tolerated in pts with advanced cancer. Future studies will fully characterize the role of EPO906 in combination with estramustine in the treatment of advanced cancers. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp. Nevada Cancer Institute; Novartis Pharmaceuticals Corp.; Vertex Novartis Pharmaceuticals Corp. Alza Novartis Pharmaceuticals
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
