Martee L Hensley1, Danielle Enserro1, Helen Hatcher1, Petronella B Ottevanger1, Anders Krarup-Hansen1, Jean-Yves Blay1, Cyril Fisher1, Katherine M Moxley1, Shashikant B Lele1, Jayanthi S Lea1, Krishnansu S Tewari1, Premal H Thaker1, Oliver Zivanovic1, David M O'Malley1, Katina Robison1, David S Miller1. 1. Martee L. Hensley, Memorial Sloan Kettering Cancer Center; Martee L. Hensley and Oliver Zivanovic, Weill Cornell Medical College, New York City; Danielle Enserro and Shashikant B. Lele, Roswell Park Comprehensive Cancer Center, Buffalo, NY; Helen Hatcher, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge; Cyril Fisher, University of Birmingham, Birmingham, United Kingdom; Petronella B. Ottevanger, Radboud University Medical Center, Nijmegen, the Netherlands; Anders Krarup-Hansen, University Hospital Copenhagen, Copenhagen, Denmark; Jean-Yves Blay, Centre Leon Berard, Lyon, France; Katherine M. Moxley, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Jayanthi S. Lea, and David S. Miller, The University of Texas Southwestern Medical Center, Dallas, TX; Krishnansu S. Tewari, University of California at Irvine, Orange, CA; Premal H. Thaker, Washington University School of Medicine, and Siteman Cancer Center, St Louis, MO; David M. O'Malley, The Ohio State University College of Medicine, Columbus, OH; Katina Robison, Women and Infants Hospital in Rhode Island, Providence, RI.
Abstract
PURPOSE: We conducted a randomized phase III trial to determine whether adjuvant chemotherapy improves survival in women with uterine leiomyosarcoma. METHODS:Women with uterus-confined, high-grade leiomyosarcoma who were confirmed disease free by imaging were randomly assigned to four cycles of gemcitabine plus docetaxel, followed by four cycles of doxorubicin, or to observation. All were followed for evidence of recurrence. The primary end point was overall survival (OS). RESULTS: With international collaboration, 38 of the targeted accrual of 216 patients were enrolled, after which the study was closed by the National Cancer Institute for accrual futility. Twenty patients were assigned to chemotherapy, 18 to observation. Among the 17 patients treated with at least one cycle of chemotherapy, grade 3 or 4 toxicities were observed in 47%; among the 18 patients assigned to observation, one had grade 3 hypertension. There were six deaths (chemotherapy, n = 5; observation, n = 1), all due to disease. The restricted mean survival time for OS was estimated as 34.3 months (95% CI, 25.3 to 43.3 months) in the chemotherapy arm and as 46.4 months (95% CI, 43.6 to 49.1 months) in the observation arm. There were eight recurrences in each arm. The restricted mean survival time for recurrence-free survival was estimated as 18.1 (95% CI, 14.2 to 22.0) months in the chemotherapy arm and as 14.6 months (95% CI, 10.3 to 19.0 months) in the observation arm. Neither survival outcome comparison was considered statistically robust, due to the small sample size. CONCLUSION: Despite international collaboration to test the role of adjuvant chemotherapy in uterine-confined leiomyosarcoma, this study was closed for accrual futility. Although the sample size precludes robust statistical comparison, observed OS and recurrence-free survival data do not show superior outcomes with adjuvant chemotherapy.
RCT Entities:
PURPOSE: We conducted a randomized phase III trial to determine whether adjuvant chemotherapy improves survival in women with uterine leiomyosarcoma. METHODS:Women with uterus-confined, high-grade leiomyosarcoma who were confirmed disease free by imaging were randomly assigned to four cycles of gemcitabine plus docetaxel, followed by four cycles of doxorubicin, or to observation. All were followed for evidence of recurrence. The primary end point was overall survival (OS). RESULTS: With international collaboration, 38 of the targeted accrual of 216 patients were enrolled, after which the study was closed by the National Cancer Institute for accrual futility. Twenty patients were assigned to chemotherapy, 18 to observation. Among the 17 patients treated with at least one cycle of chemotherapy, grade 3 or 4 toxicities were observed in 47%; among the 18 patients assigned to observation, one had grade 3 hypertension. There were six deaths (chemotherapy, n = 5; observation, n = 1), all due to disease. The restricted mean survival time for OS was estimated as 34.3 months (95% CI, 25.3 to 43.3 months) in the chemotherapy arm and as 46.4 months (95% CI, 43.6 to 49.1 months) in the observation arm. There were eight recurrences in each arm. The restricted mean survival time for recurrence-free survival was estimated as 18.1 (95% CI, 14.2 to 22.0) months in the chemotherapy arm and as 14.6 months (95% CI, 10.3 to 19.0 months) in the observation arm. Neither survival outcome comparison was considered statistically robust, due to the small sample size. CONCLUSION: Despite international collaboration to test the role of adjuvant chemotherapy in uterine-confined leiomyosarcoma, this study was closed for accrual futility. Although the sample size precludes robust statistical comparison, observed OS and recurrence-free survival data do not show superior outcomes with adjuvant chemotherapy.
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