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J Clin Oncol. 2018 Sep 20;36(27):2770-2777. doi: 10.1200/JCO.2018.77.9694. Epub 2018 Aug 9.

Addition of Vincristine and Irinotecan to Vincristine, Dactinomycin, and Cyclophosphamide Does Not Improve Outcome for Intermediate-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group.

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Douglas S. Hawkins, Erin R. Rudzinski, and Margarett Shnorhavorian, Seattle Children's Hospital, Seattle, WA; Yueh-Yun Chi and Jing Tian, University of Florida, Gainesville, FL; James R. Anderson, Merck Research Laboratories, North Wales, PA; Carola A.S. Arndt, Mayo Clinic, Rochester, MN; Lisa Bomgaars, Texas Children's Hospital; Andrea Hayes-Jordan, MD Anderson Cancer Center, Houston; Stephen X. Skapek, University of Texas Southwestern, Dallas, TX; Sarah S. Donaldson, Lynn Million, and Sheri L. Spunt, Stanford University School of Medicine, Stanford; Leo Mascarenhas and David M. Parham, Children's Hospital of Los Angeles, Los Angeles; Jeannine S. McCune, City of Hope, Duarte, CA; Mary Beth McCarville, St Jude Children's Research Hospital, Memphis, TN; Geoff McCowage, Children's Hospital at Westmead, Westmead, New South Wales, Australia; Carol D. Morris, Johns Hopkins University, Baltimore, MD, David A. Rodeberg, East Carolina University, Greenville, NC; Lisa A. Teot, Boston Children's Hospital; Torunn I. Yock, Massachusetts General Hospital, Boston, MA; Suzanne Wolden, Memorial Sloan Kettering Cancer Center, New York, NY; and William H. Meyer, University of Oklahoma Health Sciences Center, Oklahoma City, OK.


Purpose Intermediate-risk rhabdomyosarcoma (RMS) includes patients with either nonmetastatic, unresected embryonal RMS (ERMS) with an unfavorable primary site or nonmetastatic alveolar RMS (ARMS). The primary aim of this study was to improve the outcome of patients with intermediate-risk RMS by substituting vincristine and irinotecan (VI) for half of vincristine, dactinomycin, and cyclophosphamide (VAC) courses. All patients received a lower dose of cyclophosphamide and earlier radiation therapy than in previous trials. Patients and Methods Patients were randomly assigned at study entry to either VAC (cumulative cyclophosphamide dose, 16.8 g/m2) or VAC/VI (cumulative cyclophosphamide dose, 8.4 g/m2) for 42 weeks of therapy. Radiation therapy started at week 4, with individualized local control plans permitted for patients younger than 24 months. The primary study end point was event-free survival (EFS). The study design had an 80% power (5% one-sided α-level) to detect an improved long-term EFS from 65% (with VAC) to 76% (with VAC/VI). Results A total of 448 eligible patients were enrolled in the study. At a median follow-up of 4.8 years, the 4-year EFS was 63% with VAC and 59% with VAC/VI ( P = .51), and 4-year overall survival was 73% for VAC and 72% for VAC/VI ( P = .80). Within the ARMS and ERMS subgroups, no difference in outcome by treatment arm was found. Severe hematologic toxicity was less common with VAC/VI therapy. Conclusion The addition of VI to VAC did not improve EFS or OS for patients with intermediate-risk RMS. VAC/VI had less hematologic toxicity and a lower cumulative cyclophosphamide dose, making VAC/VI an alternative standard therapy for intermediate-risk RMS.


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