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

Douglas S. Hawkins, Yueh Yun Chi, James R. Anderson, Jing Tian, Carola A.S. Arndt, Lisa Bomgaars, Sarah S. Donaldson, Andrea Hayes-Jordan, Leo Mascarenhas, Mary Beth Mccarville, Jeannine S. Mccune, Geoff Mccowage, Lynn Million, Carol D. Morris, David M. Parham, David A. Rodeberg, Erin R. Rudzinski, Margarett Shnorhavorian, Sheri L. Spunt, Stephen X. Skapek & 4 others Lisa A. Teot, Suzanne Wolden, Torunn I. Yock, William H. Meyer

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Abstract

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 a-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.

Original languageEnglish (US)
Pages (from-to)2770-2777
Number of pages8
JournalJournal of Clinical Oncology
Volume36
Issue number27
DOIs
StatePublished - Sep 20 2018

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irinotecan
Rhabdomyosarcoma
Dactinomycin
Vincristine
Cyclophosphamide
Disease-Free Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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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. / Hawkins, Douglas S.; Chi, Yueh Yun; Anderson, James R.; Tian, Jing; Arndt, Carola A.S.; Bomgaars, Lisa; Donaldson, Sarah S.; Hayes-Jordan, Andrea; Mascarenhas, Leo; Mccarville, Mary Beth; Mccune, Jeannine S.; Mccowage, Geoff; Million, Lynn; Morris, Carol D.; Parham, David M.; Rodeberg, David A.; Rudzinski, Erin R.; Shnorhavorian, Margarett; Spunt, Sheri L.; Skapek, Stephen X.; Teot, Lisa A.; Wolden, Suzanne; Yock, Torunn I.; Meyer, William H.

In: Journal of Clinical Oncology, Vol. 36, No. 27, 20.09.2018, p. 2770-2777.

Research output: Contribution to journalArticle

Hawkins, DS, Chi, YY, Anderson, JR, Tian, J, Arndt, CAS, Bomgaars, L, Donaldson, SS, Hayes-Jordan, A, Mascarenhas, L, Mccarville, MB, Mccune, JS, Mccowage, G, Million, L, Morris, CD, Parham, DM, Rodeberg, DA, Rudzinski, ER, Shnorhavorian, M, Spunt, SL, Skapek, SX, Teot, LA, Wolden, S, Yock, TI & Meyer, WH 2018, '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', Journal of Clinical Oncology, vol. 36, no. 27, pp. 2770-2777. https://doi.org/10.1200/JCO.2018.77.9694
Hawkins, Douglas S. ; Chi, Yueh Yun ; Anderson, James R. ; Tian, Jing ; Arndt, Carola A.S. ; Bomgaars, Lisa ; Donaldson, Sarah S. ; Hayes-Jordan, Andrea ; Mascarenhas, Leo ; Mccarville, Mary Beth ; Mccune, Jeannine S. ; Mccowage, Geoff ; Million, Lynn ; Morris, Carol D. ; Parham, David M. ; Rodeberg, David A. ; Rudzinski, Erin R. ; Shnorhavorian, Margarett ; Spunt, Sheri L. ; Skapek, Stephen X. ; Teot, Lisa A. ; Wolden, Suzanne ; Yock, Torunn I. ; Meyer, William H. / 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. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 27. pp. 2770-2777.
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title = "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",
abstract = "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 a-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.",
author = "Hawkins, {Douglas S.} and Chi, {Yueh Yun} and Anderson, {James R.} and Jing Tian and Arndt, {Carola A.S.} and Lisa Bomgaars and Donaldson, {Sarah S.} and Andrea Hayes-Jordan and Leo Mascarenhas and Mccarville, {Mary Beth} and Mccune, {Jeannine S.} and Geoff Mccowage and Lynn Million and Morris, {Carol D.} and Parham, {David M.} and Rodeberg, {David A.} and Rudzinski, {Erin R.} and Margarett Shnorhavorian and Spunt, {Sheri L.} and Skapek, {Stephen X.} and Teot, {Lisa A.} and Suzanne Wolden and Yock, {Torunn I.} and Meyer, {William H.}",
year = "2018",
month = "9",
day = "20",
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language = "English (US)",
volume = "36",
pages = "2770--2777",
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TY - JOUR

T1 - Addition of vincristine and irinotecan to vincristine, dactinomycin, and cyclophosphamide does not improve outcome for intermediate-risk rhabdomyosarcoma

T2 - A report from the children’s oncology group

AU - Hawkins, Douglas S.

AU - Chi, Yueh Yun

AU - Anderson, James R.

AU - Tian, Jing

AU - Arndt, Carola A.S.

AU - Bomgaars, Lisa

AU - Donaldson, Sarah S.

AU - Hayes-Jordan, Andrea

AU - Mascarenhas, Leo

AU - Mccarville, Mary Beth

AU - Mccune, Jeannine S.

AU - Mccowage, Geoff

AU - Million, Lynn

AU - Morris, Carol D.

AU - Parham, David M.

AU - Rodeberg, David A.

AU - Rudzinski, Erin R.

AU - Shnorhavorian, Margarett

AU - Spunt, Sheri L.

AU - Skapek, Stephen X.

AU - Teot, Lisa A.

AU - Wolden, Suzanne

AU - Yock, Torunn I.

AU - Meyer, William H.

PY - 2018/9/20

Y1 - 2018/9/20

N2 - 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 a-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.

AB - 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 a-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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U2 - 10.1200/JCO.2018.77.9694

DO - 10.1200/JCO.2018.77.9694

M3 - Article

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JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

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