Carolyn K McCourt1, Wei Deng2, Don S Dizon3, Heather A Lankes4, Michael J Birrer5, Michele M Lomme6, Matthew A Powell7, James E Kendrick8, Joel N Saltzman9, David Warshal10, Meaghan E Tenney11, David M Kushner12, Carol Aghajanian13. 1. Dept. of Gynecologic Oncology, Washington University School of Medicine, Saint Louis, MO 63110, United States. Electronic address: mccourtc@wudosis.wustl.edu. 2. NRG Oncology Statistics & Data Management Center, Roswell Park Cancer Institute, Buffalo, NY 14263, United States. Electronic address: wdeng@gogstats.org. 3. Dept. of Gynecologic Oncology, Massachusetts General Hospital Cancer Center, Boston, MA 02114, United States. Electronic address: ddizon@mgh.harvard.edu. 4. NRG Oncology Statistics & Data Management Center, Roswell Park Cancer Institute, Buffalo, NY 14263, United States. Electronic address: hlankes@gogstats.org. 5. Dept. of Gynecologic Oncology, Massachusetts General Hospital Cancer Center, Boston, MA 02114, United States. Electronic address: mbirrer@partners.org. 6. Dept. of Pathology, Women & Infants Hospital of Rhode Island, Providence, RI 02905, United States. Electronic address: mlomme@wihri.org. 7. Dept. of Obstetrics & Gynecology, Washington University School of Medicine, Saint Louis, MO 63110, United States. Electronic address: mpowell@wustl.edu. 8. Dept. of Gynecologic Oncology, Florida Hospital Cancer Institute CCOP, Orlando, FL 32804, United States. Electronic address: tkendrick2@gmail.com. 9. Dept. of Oncology & Hematology, Lake University Ireland Cancer Center, Mentor, OH 44060, United States. Electronic address: Joel.Saltzman@uhhospitals.org. 10. Dept. of Gynecologic Oncology, Cooper Health, Camden, NJ 08103, United States. Electronic address: warshal-david@cooperhealth.edu. 11. Section of Gynecologic Oncology, University of Chicago, Chicago, IL 60637, United States. Electronic address: meaghan.tenney@northside.com. 12. Dept. of Gynecologic Oncology, University of Wisconsin-Madison, Madison, WI 53792, United States. Electronic address: dmkushner@wisc.edu. 13. Dept. of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, United States. Electronic address: aghajanc@mskcc.org.
Abstract
BACKGROUND: The primary objectives were to determine the objective response rate (ORR) and safety profile of ixabepilone in women with recurrent or persistent uterine carcinosarcoma (UCS). Secondary objectives included progression-free survival (PFS) and overall survival (OS). Exploratory translational objectives included characterization of class III beta tubulin expression and its association with response, PFS, and OS. METHODS: Patients had measurable disease; up to two prior chemotherapeutic regimens were allowed, but must have included a taxane. Women received ixabepilone 40mg/m2 as a 3hour IV infusion on day 1 of a 21daycycle. Treatment was continued until disease progression or unacceptable toxicity occurred. RESULTS: Forty-two women were enrolled, with 34 eligible and evaluable. Median age was 68years. ECOG performance status was 0 in 56% of women, 38% had received radiation, and 15% had received 2 lines of chemotherapy. Overall ORR was 11.8% (4/34, 90% CI 4.2-25.1%); all were partial responses. Stable disease for at least 8weeks was achieved in 8 patients (23.5%). Median PFS and OS were 1.7mo and 7.7mo, respectively, with a median follow-up of 37mo. Six month PFS was 20.6%. Major grade≥3 toxicities were neutropenia (47%), fatigue (15%), dehydration (15%), hypertension (15%), and hyponatremia (15%); grade 2 peripheral neuropathy was reported in 18%. In this small sample size, class III beta tubulin expression in the primary tumor was not associated with the response to ixabepilone, PFS, or OS. CONCLUSION: In this cohort of women, single agent ixabepilone showed modest but insufficient clinical activity.
BACKGROUND: The primary objectives were to determine the objective response rate (ORR) and safety profile of ixabepilone in women with recurrent or persistent uterine carcinosarcoma (UCS). Secondary objectives included progression-free survival (PFS) and overall survival (OS). Exploratory translational objectives included characterization of class III beta tubulin expression and its association with response, PFS, and OS. METHODS:Patients had measurable disease; up to two prior chemotherapeutic regimens were allowed, but must have included a taxane. Women received ixabepilone 40mg/m2 as a 3hour IV infusion on day 1 of a 21daycycle. Treatment was continued until disease progression or unacceptable toxicity occurred. RESULTS: Forty-two women were enrolled, with 34 eligible and evaluable. Median age was 68years. ECOG performance status was 0 in 56% of women, 38% had received radiation, and 15% had received 2 lines of chemotherapy. Overall ORR was 11.8% (4/34, 90% CI 4.2-25.1%); all were partial responses. Stable disease for at least 8weeks was achieved in 8 patients (23.5%). Median PFS and OS were 1.7mo and 7.7mo, respectively, with a median follow-up of 37mo. Six month PFS was 20.6%. Major grade≥3 toxicities were neutropenia (47%), fatigue (15%), dehydration (15%), hypertension (15%), and hyponatremia (15%); grade 2 peripheral neuropathy was reported in 18%. In this small sample size, class III beta tubulin expression in the primary tumor was not associated with the response to ixabepilone, PFS, or OS. CONCLUSION: In this cohort of women, single agent ixabepilone showed modest but insufficient clinical activity.
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