Patrick J Leavey1, Nadia N Laack2, Mark D Krailo3, Allen Buxton4, R Lor Randall5, Steven G DuBois6, Damon R Reed7, Holcombe E Grier6, Douglas S Hawkins8, Bruce Pawel9, Helen Nadel10, Richard B Womer11, G Douglas Letson7, Mark Bernstein12, Kenneth Brown13, Alexis Maciej14, Paul Chuba15, Atif A Ahmed16, Daniel J Indelicato17, Dian Wang18, Neyssa Marina19, Richard Gorlick20, Katherine A Janeway6, Leo Mascarenhas9. 1. UT Southwestern Medical Center Dallas and Children's Health, Children's Medical Center Dallas, Dallas, TX. 2. Mayo Clinic, Rochester, MN. 3. University of Southern California, Los Angeles, CA. 4. Children's Oncology, Operations Office, Monrovia, CA. 5. UC Davis, Sacramento, CA. 6. Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA. 7. Moffitt Cancer Center Adolescent and Young Adult Program, Tampa, FL. 8. Seattle Children's Hospital, Seattle, WA. 9. Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA. 10. Lucile Packard Children's Hospital Stanford University, Palo Alto, CA. 11. Children's Hospital of Philadelphia, Philadelphia, PA. 12. IWK Health Center, Halifax, NS. 13. British Columbia Children's Hospital, Vancouver, BC, Canada. 14. University of Minnesota Medical Center, Minneapolis, MN. 15. St John Hospital and Medical Center, Grosse Pointe, MI. 16. The Children's Mercy Hospital, Kansas City, MO. 17. University of Florida, Jacksonville, FL. 18. Rush University Medical Center, Chicago, IL. 19. Stanford University School of Medicine, Lucile Packard Children's Hospital, Stanford, CA. 20. MD Anderson Cancer Center, Houston, TX.
Abstract
PURPOSE: The primary aim of this phase III randomized trial was to test whether the addition of vincristine, topotecan, and cyclophosphamide (VTC) to interval compressed chemotherapy improved survival outcomes for patients with previously untreated nonmetastatic Ewing sarcoma. METHODS: Patients were randomly assigned to receive standard five-drug interval compressed chemotherapy (regimen A) for 17 cycles or experimental therapy with five cycles of VTC within the 17 cycles (regimen B). Patients were stratified by age at diagnosis (< 18 years and ≥18 years) and tumor site (pelvic bone, nonpelvic bone, and extraosseous). Tumor volume at diagnosis was categorized as < 200 mL or ≥ 200 mL. Local control occurred following six cycles. Histologic response was categorized as no viable or any viable tumor. Event-free survival (EFS) and overall survival (OS) were compared between randomized groups with stratified log-rank tests. RESULTS: Of 642 enrolled patients, 309 eligible patients received standard and 320 received experimental therapy. The 5-year EFS and OS were 78% and 87%, respectively. There was no difference in survival outcomes between randomized groups (5-year EFS regimen A v regimen B, 78% v 79%; P = .192; 5-year OS 86% v 88%; P = .159). Age and primary site did not affect the risk of an EFS event. However, age ≥ 18 years was associated with an increased risk of death at 5 years (hazard ratio 1.84; 95% CI, 1.15 to 2.96; P = .009). The 5-year EFS rates for patients with pelvic, nonpelvic bone, and extraosseous primary tumors were 75%, 78%, and 85%, respectively. Tumor volume ≥ 200 mL was significantly associated with lower EFS. CONCLUSION: While VTC added to five-drug interval compressed chemotherapy did not improve survival, these outcomes represent the best survival estimates to date for patients with previously untreated nonmetastatic Ewing sarcoma.
PURPOSE: The primary aim of this phase III randomized trial was to test whether the addition of vincristine, topotecan, and cyclophosphamide (VTC) to interval compressed chemotherapy improved survival outcomes for patients with previously untreated nonmetastatic Ewing sarcoma. METHODS: Patients were randomly assigned to receive standard five-drug interval compressed chemotherapy (regimen A) for 17 cycles or experimental therapy with five cycles of VTC within the 17 cycles (regimen B). Patients were stratified by age at diagnosis (< 18 years and ≥18 years) and tumor site (pelvic bone, nonpelvic bone, and extraosseous). Tumor volume at diagnosis was categorized as < 200 mL or ≥ 200 mL. Local control occurred following six cycles. Histologic response was categorized as no viable or any viable tumor. Event-free survival (EFS) and overall survival (OS) were compared between randomized groups with stratified log-rank tests. RESULTS: Of 642 enrolled patients, 309 eligible patients received standard and 320 received experimental therapy. The 5-year EFS and OS were 78% and 87%, respectively. There was no difference in survival outcomes between randomized groups (5-year EFS regimen A v regimen B, 78% v 79%; P = .192; 5-year OS 86% v 88%; P = .159). Age and primary site did not affect the risk of an EFS event. However, age ≥ 18 years was associated with an increased risk of death at 5 years (hazard ratio 1.84; 95% CI, 1.15 to 2.96; P = .009). The 5-year EFS rates for patients with pelvic, nonpelvic bone, and extraosseous primary tumors were 75%, 78%, and 85%, respectively. Tumor volume ≥ 200 mL was significantly associated with lower EFS. CONCLUSION: While VTC added to five-drug interval compressed chemotherapy did not improve survival, these outcomes represent the best survival estimates to date for patients with previously untreated nonmetastatic Ewing sarcoma.
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Authors: David S Shulman; Sarah B Whittle; Didier Surdez; Kelly M Bailey; Enrique de Álava; Jason T Yustein; Adam Shlien; Masanori Hayashi; Alexander J R Bishop; Brian D Crompton; Steven G DuBois; Neerav Shukla; Patrick J Leavey; Stephen L Lessnick; Heinrich Kovar; Olivier Delattre; Thomas G P Grünewald; Cristina R Antonescu; Ryan D Roberts; Jeffrey A Toretsky; Franck Tirode; Richard Gorlick; Katherine A Janeway; Damon Reed; Elizabeth R Lawlor; Patrick J Grohar Journal: NPJ Precis Oncol Date: 2022-09-17