Linda R Duska1, John A Blessing2, Jacob Rotmensch3, Robert S Mannel4, Parviz Hanjani5, Peter G Rose6, Don S Dizon7. 1. University of Virginia Health Systems, Division of Gynecology Oncology, P.O. Box 800712, Charlottesville, VA 22908, USA. Electronic address: lduska@virginia.edu. 2. Gynecologic Oncology Group, Statistical & Data Center, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263, USA. Electronic address: blessing@gogstats.org. 3. Rush-Presbyterian St. Luke's Medical Center, 1725 W. Harrison, Suite 842 Professional Bldg., Chicago, IL 60612, USA. Electronic address: jacob_rotmensch@rush.edu. 4. The Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, 800 NE 10th Street, Oklahoma City, OK 73104, USA. Electronic address: Robert-mannel@ouhsc.edu. 5. Hanjani Institute for Gynecologic Oncology, Abington Memorial Hospital, 1 Widener, 1200 Old York Road, Abington, PA 19001, USA. Electronic address: phanjani@amh.org. 6. Cleveland Clinic, 9500 Euclid Ave./A81, Cleveland, OH 44195, USA. Electronic address: rosep@ccf.org. 7. Massachusetts General Hospital, GYN Oncology, 55 Fruit St., Yawkey 9E, Boston, MA 02114, USA. Electronic address: ddizon@partners.org.
Abstract
OBJECTIVE: The combination of gemcitabine and docetaxel is the standard first-line therapy for recurrent or metastatic uterine leiomyosarcoma. There is no standard second-line therapy. Ixabepilone is a semi-synthetic analog of epothilone B that binds to the same site on beta tubulin as paclitaxel and may be a more potent polymerizer of tubulin. We sought to determine the activity of ixabepilone as a single agent as second-line treatment for patients with metastatic uterine leiomyosarcoma who had received taxane based therapy. METHODS: Eligible women with unresectable uterine leiomyosarcoma progressing after prior cytotoxic therapy containing a taxane were treated with ixabepilone 40 mg/m(2) on day one of a 21 day cycle. Patients with prior pelvic radiation were treated without dose reduction. Response Evaluation Criteria in Solid Tumors (RECIST) response was assessed by computed tomography (CT). RESULTS: Twenty-three of 26 women were evaluable (two wrong histology, one never treated) with two of 23 receiving 1 cycle of therapy. There were no complete or partial responses. Stable disease (SD) was seen in four patients (17.4%, median 3.4 months). Seventeen patients (73.9%) had increasing disease (PD) and two patients were inevaluable per RECIST. One patient had SD over 6 cycles of treatment. Median PFS for all 23 patients was 1.4 months and overall survival was 7.0 months. The predominant grade 3 or 4 toxicity was uncomplicated myelosuppression: neutropenia grade 3 (13%), grade 4 (17%), and anemia grade 3 (22%). CONCLUSION: Ixabepilone as a single agent is not an active second-line therapy for uterine leiomyosarcoma previously treated with a taxane.
OBJECTIVE: The combination of gemcitabine and docetaxel is the standard first-line therapy for recurrent or metastatic uterine leiomyosarcoma. There is no standard second-line therapy. Ixabepilone is a semi-synthetic analog of epothilone B that binds to the same site on beta tubulin as paclitaxel and may be a more potent polymerizer of tubulin. We sought to determine the activity of ixabepilone as a single agent as second-line treatment for patients with metastatic uterine leiomyosarcoma who had received taxane based therapy. METHODS: Eligible women with unresectable uterine leiomyosarcoma progressing after prior cytotoxic therapy containing a taxane were treated with ixabepilone 40 mg/m(2) on day one of a 21 day cycle. Patients with prior pelvic radiation were treated without dose reduction. Response Evaluation Criteria in Solid Tumors (RECIST) response was assessed by computed tomography (CT). RESULTS: Twenty-three of 26 women were evaluable (two wrong histology, one never treated) with two of 23 receiving 1 cycle of therapy. There were no complete or partial responses. Stable disease (SD) was seen in four patients (17.4%, median 3.4 months). Seventeen patients (73.9%) had increasing disease (PD) and two patients were inevaluable per RECIST. One patient had SD over 6 cycles of treatment. Median PFS for all 23 patients was 1.4 months and overall survival was 7.0 months. The predominant grade 3 or 4 toxicity was uncomplicated myelosuppression: neutropenia grade 3 (13%), grade 4 (17%), and anemia grade 3 (22%). CONCLUSION:Ixabepilone as a single agent is not an active second-line therapy for uterine leiomyosarcoma previously treated with a taxane.
Authors: Winette T A van der Graaf; Jean-Yves Blay; Sant P Chawla; Dong-Wan Kim; Binh Bui-Nguyen; Paolo G Casali; Patrick Schöffski; Massimo Aglietta; Arthur P Staddon; Yasuo Beppu; Axel Le Cesne; Hans Gelderblom; Ian R Judson; Nobuhito Araki; Monia Ouali; Sandrine Marreaud; Rachel Hodge; Mohammed R Dewji; Corneel Coens; George D Demetri; Christopher D Fletcher; Angelo Paolo Dei Tos; Peter Hohenberger Journal: Lancet Date: 2012-05-16 Impact factor: 79.321
Authors: Francis Y F Lee; Richard Smykla; Kathy Johnston; Krista Menard; Kelly McGlinchey; Russell W Peterson; Amy Wiebesiek; Gregory Vite; Craig R Fairchild; Robert Kramer Journal: Cancer Chemother Pharmacol Date: 2008-03-19 Impact factor: 3.333
Authors: Martee L Hensley; J Kyle Wathen; Robert G Maki; Dejka M Araujo; Gregory Sutton; Dennis A Priebat; Suzanne George; Robert A Soslow; Laurence H Baker Journal: Cancer Date: 2013-01-18 Impact factor: 6.860
Authors: Jocelyn Reader; Amy K Harper; Teklu Legesse; Paul N Staats; Olga Goloubeva; Gautam G Rao; Amy Fulton; Dana M Roque Journal: Cancers (Basel) Date: 2019-10-18 Impact factor: 6.639