Joanne P Lagmay1, Mark D Krailo2, Ha Dang2, AeRang Kim2, Douglas S Hawkins2, Orren Beaty2, Brigitte C Widemann2, Theodore Zwerdling2, Lisa Bomgaars2, Anne-Marie Langevin2, Holcombe E Grier2, Brenda Weigel2, Susan M Blaney2, Richard Gorlick2, Katherine A Janeway2. 1. Joanne P. Lagmay, Shands Hospital for Children, University of Florida, Gainesville, FL; Mark D. Krailo and Ha Dang, University of Southern California, Los Angeles; and Children's Oncology Group, Monrovia; Theodore Zwerdling, Jonathan Jaques Children's Cancer Center, Miller Children's and Women's Hospital, Long Beach, CA; AeRang Kim, Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC; Douglas S. Hawkins, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA; Orren Beaty III, Zeiss Children's Cancer Center, Mission Hospitals, Asheville, NC; Brigitte C. Widemann, National Institutes of Health Clinical Center, Bethesda, MD; Lisa Bomgaars and Susan M. Blaney, Baylor College of Medicine/Texas Children's Cancer Center, Houston; Anne-Marie Langevin, University of Texas Health Science Center at San Antonio, San Antonio, TX; Holcombe E. Grier and Katherine A. Janeway, Dana-Farber Cancer Institute, Boston Children's Cancer and Blood Disorders Center, Boston, MA; Brenda Weigel, University of Minnesota, Minneapolis, MN; and Richard Gorlick, The Albert Einstein College of Medicine of Yeshiva University, The Children's Hospital at Montefiore, New York, NY. jplagmay@peds.ufl.edu. 2. Joanne P. Lagmay, Shands Hospital for Children, University of Florida, Gainesville, FL; Mark D. Krailo and Ha Dang, University of Southern California, Los Angeles; and Children's Oncology Group, Monrovia; Theodore Zwerdling, Jonathan Jaques Children's Cancer Center, Miller Children's and Women's Hospital, Long Beach, CA; AeRang Kim, Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC; Douglas S. Hawkins, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA; Orren Beaty III, Zeiss Children's Cancer Center, Mission Hospitals, Asheville, NC; Brigitte C. Widemann, National Institutes of Health Clinical Center, Bethesda, MD; Lisa Bomgaars and Susan M. Blaney, Baylor College of Medicine/Texas Children's Cancer Center, Houston; Anne-Marie Langevin, University of Texas Health Science Center at San Antonio, San Antonio, TX; Holcombe E. Grier and Katherine A. Janeway, Dana-Farber Cancer Institute, Boston Children's Cancer and Blood Disorders Center, Boston, MA; Brenda Weigel, University of Minnesota, Minneapolis, MN; and Richard Gorlick, The Albert Einstein College of Medicine of Yeshiva University, The Children's Hospital at Montefiore, New York, NY.
Abstract
PURPOSE: The use of radiographic response as the primary end point in phase II osteosarcoma trials may limit optimal detection of treatment response because of the calcified tumor matrix. We performed this study to determine if time to progression could be used as an end point for subsequent studies. PATIENTS AND METHODS: We performed a retrospective analysis of outcome for patients with recurrent/refractory osteosarcoma enrolled in one of seven phase II trials conducted by the Children's Oncology Group and predecessor groups from 1997 to 2007. All trials used RECIST or WHO radiographic response criteria and the primary end point of response rate. The following potential prognostic factors-age, trial, number of prior chemotherapy regimens, sex, and race/ethnicity-were evaluated for their impact on event-free survival (EFS). We used data from a phase II study (AOST0221) of patients with osteosarcoma who were given inhaled granulocyte-macrophage colony-stimulating factor with first pulmonary recurrence who had an EFS as well as biologic end point to determine the historical disease control rate for patients with fully resected disease. RESULTS: In each included trial, the drugs tested were determined to be inactive on the basis of radiographic response rates. The EFS for 96 patients with osteosarcoma and measurable disease was 12% at 4 months (95% CI, 6% to 19%). There was no significant difference in EFS across trials according to number of prior treatment regimens or patient age, sex, and ethnicity. The 12-month EFS for the 42 evaluable patients enrolled in AOST0221 was 20% (95% CI, 10% to 34%). CONCLUSION: The EFS was uniformly poor for children with recurrent/refractory osteosarcoma in these single-arm phase II trials. We have now constructed baseline EFS outcomes that can be used as a comparison for future phase II trials for recurrent osteosarcoma.
PURPOSE: The use of radiographic response as the primary end point in phase II osteosarcoma trials may limit optimal detection of treatment response because of the calcified tumor matrix. We performed this study to determine if time to progression could be used as an end point for subsequent studies. PATIENTS AND METHODS: We performed a retrospective analysis of outcome for patients with recurrent/refractory osteosarcoma enrolled in one of seven phase II trials conducted by the Children's Oncology Group and predecessor groups from 1997 to 2007. All trials used RECIST or WHO radiographic response criteria and the primary end point of response rate. The following potential prognostic factors-age, trial, number of prior chemotherapy regimens, sex, and race/ethnicity-were evaluated for their impact on event-free survival (EFS). We used data from a phase II study (AOST0221) of patients with osteosarcoma who were given inhaled granulocyte-macrophage colony-stimulating factor with first pulmonary recurrence who had an EFS as well as biologic end point to determine the historical disease control rate for patients with fully resected disease. RESULTS: In each included trial, the drugs tested were determined to be inactive on the basis of radiographic response rates. The EFS for 96 patients with osteosarcoma and measurable disease was 12% at 4 months (95% CI, 6% to 19%). There was no significant difference in EFS across trials according to number of prior treatment regimens or patient age, sex, and ethnicity. The 12-month EFS for the 42 evaluable patients enrolled in AOST0221 was 20% (95% CI, 10% to 34%). CONCLUSION: The EFS was uniformly poor for children with recurrent/refractory osteosarcoma in these single-arm phase II trials. We have now constructed baseline EFS outcomes that can be used as a comparison for future phase II trials for recurrent osteosarcoma.
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