Rhabdomyosarcoma

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Note: these are regimens tested in subtype-specific populations, please see the main soft tissue sarcoma page for other regimens. Pleomorphic rhabdomyosarcoma is typically treated the same as soft tissue sarcoma.
Note: certain regimens are to be found on dedicated pages:
*Pediatric rhabdomyosarcoma
Last updated on 2024-09-06:4 regimens on this page
4 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Soft Tissue Sarcoma.
=Adjuvant therapy=
==VA==
VA: Vincristine & Actinomycin D
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Maurer et al. 1993 (IRS-II)	1978-1984 	Phase 3 (C)	VAC 	Did not meet co-primary endpoints of DFS/OS
Crist et al. 1995 (IRS-III)	1984-1991 	Phase 3 (C)	VAC 	Did not meet primary endpoint of PFS
Note: reported efficacy is for group I favorable-histology tumors.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Vincristine (Oncovin) as follows:
**Cycle 1: 2 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78 (12 doses)
*Dactinomycin (Cosmegen) 0.015 mg/kg (maximum dose of 0.5 mg) IV once per day on days 1 to 5
12-week cycle for 5 cycles
===References===
# IRS-II: Maurer HM, Gehan EA, Beltangady M, Crist W, Dickman PS, Donaldson SS, Fryer C, Hammond D, Hays DM, Herrmann J, Heyn R, Jones PM, Lawrence W, Newton W, Ortega J, Ragab AH, Raney RB, Ruymann FB, Soule E, Tefft M, Webber B, Wiener E, Wharam M, Vietti TJ. The Intergroup Rhabdomyosarcoma Study-II. Cancer. 1993 Mar 1;71(5):1904-22. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# IRS-III: Crist W, Gehan EA, Ragab AH, Dickman PS, Donaldson SS, Fryer C, Hammond D, Hays DM, Herrmann J, Heyn R, Jones PM, Lawrence W, Newton W, Ortega J, Raney RB, Ruymann FB, Tefft M, Webber B, Wiener E, Wharam M, Vietti TJ, Maurer HM. The Third Intergroup Rhabdomyosarcoma Study. J Clin Oncol. 1995 Mar;13(3):610-30. link to original article EuroPMC
=All lines of therapy=
==VAC==
VAC: Vincristine, Actinomycin D, Cyclophosphamide
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Maurer et al. 1988 (IRS-I) 	1972-1978 	Phase 3 (C) 	VAC & RT 	Did not meet co-primary endpoints of DFS/OS
Crist et al. 1995 (IRS-III) 	1984-1991 	Phase 3 (E-RT-esc) 	VA 	Did not meet primary endpoint of PFS
Crist et al. 2001 (IRS-IV) 	1991-1997 	Phase 3 (E-switch-ic)	1. VAI 	Did not meet co-primary endpoints of FFS/OS
Crist et al. 2001 (IRS-IV) 	1991-1997 	Phase 3 (E-switch-ic)	2. VIE 	Did not meet co-primary endpoints of FFS/OS
Arndt et al. 2009 (COG D9803) 	1999-2005 	Phase 3 (C) 	VAC/VTC 	Did not meet primary endpoint of FFS
Hawkins et al. 2018 (COG ARST0531)	2006-2012 	Phase 3 (C) 	VAC/VI 	Did not meet primary endpoint of EFS
Note: The first week of this protocol is week 0.
====Chemotherapy====
*Vincristine (Oncovin) as follows:
**Weeks 0 to 11: 2 mg/m2 (maximum dose of 2 mg) IV once on day 1
*Dactinomycin (Cosmegen) as follows:
**Weeks 0, 12, 24, 36, 48: 0.015 mg/kg IV once per day on days 1 to 5
*Cyclophosphamide (Cytoxan) as follows:
**Weeks 6 to 103: 2.5 mg/kg PO once per day on days 1 to 7
104-week course
===References===
# IRS-I: Maurer HM, Moon T, Donaldson M, Fernandez C, Gehan EA, Hammond D, Hays DM, Lawrence W Jr, Newton W, Ragab A, Raney B, Soule EH, Sutow WW, Tefft M. The intergroup rhabdomyosarcoma study: a preliminary report. Cancer. 1977 Nov;40(5):2015-26. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
##Update: Maurer HM, Beltangady M, Gehan EA, Crist W, Hammond D, Hays DM, Heyn R, Lawrence W, Newton W, Ortega J, Ragab AH, Raney RB, Ruymann FB, Soule E, Tefft M, Webber B, Wharam M, Vietti TJ. The Intergroup Rhabdomyosarcoma Study-I: a final report. Cancer. 1988 Jan 15;61(2):209-20. link to original article EuroPMC
# IRS-III: Crist W, Gehan EA, Ragab AH, Dickman PS, Donaldson SS, Fryer C, Hammond D, Hays DM, Herrmann J, Heyn R, Jones PM, Lawrence W, Newton W, Ortega J, Raney RB, Ruymann FB, Tefft M, Webber B, Wiener E, Wharam M, Vietti TJ, Maurer HM. The Third Intergroup Rhabdomyosarcoma Study. J Clin Oncol. 1995 Mar;13(3):610-30. link to original article EuroPMC
# IRS-IV: Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, Breneman J, Qualman SJ, Wiener E, Wharam M, Lobe T, Webber B, Maurer HM, Donaldson SS. Intergroup Rhabdomyosarcoma Study-IV: results for patients with nonmetastatic disease. J Clin Oncol. 2001 Jun 15;19(12):3091-102. link to original article EuroPMC
# COG D9803: Arndt CA, Stoner JA, Hawkins DS, Rodeberg DA, Hayes-Jordan AA, Paidas CN, Parham DM, Teot LA, Wharam MD, Breneman JC, Donaldson SS, Anderson JR, Meyer WH. Vincristine, actinomycin, and cyclophosphamide compared with vincristine, actinomycin, and cyclophosphamide alternating with vincristine, topotecan, and cyclophosphamide for intermediate-risk rhabdomyosarcoma: Children's Oncology Group study D9803. J Clin Oncol. 2009 Nov 1;27(31):5182-8. Epub 2009 Sep 21. link to original article link to PMC article EuroPMC NCT00003958
# COG ARST0531: 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; Children's Oncology Group. 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. J Clin Oncol. 2018 Sep 20;36(27):2770-2777. Epub 2018 Aug 9. link to original article link to PMC article EuroPMC NCT00354835
==VAI==
VAI: Vincristine, Actinomycin-D (Dactinomycin), Ifosfamide
IVA: Ifosfamide, Vincristine, Actinomycin-D (Dactinomycin)
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Crist et al. 2001 (IRS-IV) 	1991-1997 	Phase 3 (E-switch-ic)	1. VAC 	Did not meet co-primary endpoints of FFS/OS
Crist et al. 2001 (IRS-IV) 	1991-1997 	Phase 3 (E-switch-ic)	2. VIE 	Did not meet co-primary endpoints of FFS/OS
Oberlin et al. 2012 (SIOP MMT95) 	1995-2003 	Phase 3 (C) 	IVA/CEV/IVE	Did not meet primary endpoint of OS
Bisogno et al. 2018 (EpSSG RMS 2005)	2006-2016 	Phase 3 (C) 	IVA-D-IVA 	Did not meet primary endpoint of EFS36
====Chemotherapy====
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15
*Dactinomycin (Cosmegen) 0.015 mg/kg IV once per day on days 1 to 5
*Ifosfamide (Ifex) 1800 mg/m2 IV once per day on days 1 to 5
====Supportive therapy====
*Mesna (Mesnex)
21-day cycle for 3 cycles
====Subsequent treatment====
*VI & RT consolidation
===References===
# IRS-IV: Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, Breneman J, Qualman SJ, Wiener E, Wharam M, Lobe T, Webber B, Maurer HM, Donaldson SS. Intergroup Rhabdomyosarcoma Study-IV: results for patients with nonmetastatic disease. J Clin Oncol. 2001 Jun 15;19(12):3091-102. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# SIOP MMT95: Oberlin O, Rey A, Sanchez de Toledo J, Martelli H, Jenney ME, Scopinaro M, Bergeron C, Merks JH, Bouvet N, Ellershaw C, Kelsey A, Spooner D, Stevens MC. Randomized comparison of intensified six-drug versus standard three-drug chemotherapy for high-risk nonmetastatic rhabdomyosarcoma and other chemotherapy-sensitive childhood soft tissue sarcomas: long-term results from the International Society of Pediatric Oncology MMT95 study. J Clin Oncol. 2012 Jul 10;30(20):2457-65. Epub 2012 Jun 4. link to original article EuroPMC NCT00002898
# EpSSG RMS 2005: Bisogno G, Jenney M, Bergeron C, Gallego Melcón S, Ferrari A, Oberlin O, Carli M, Stevens M, Kelsey A, De Paoli A, Gaze MN, Martelli H, Devalck C, Merks JH, Ben-Arush M, Glosli H, Chisholm J, Orbach D, Minard-Colin V, De Salvo GL; European paediatric Soft tissue sarcoma Study Group. Addition of dose-intensified doxorubicin to standard chemotherapy for rhabdomyosarcoma (EpSSG RMS 2005): a multicentre, open-label, randomised controlled, phase 3 trial. Lancet Oncol. 2018 Aug;19(8):1061-1071. Epub 2018 Jun 22. link to original article EuroPMC NCT00339118
## Update: Bisogno G, De Salvo GL, Bergeron C, Gallego Melcón S, Merks JH, Kelsey A, Martelli H, Minard-Colin V, Orbach D, Glosli H, Chisholm J, Casanova M, Zanetti I, Devalck C, Ben-Arush M, Mudry P, Ferman S, Jenney M, Ferrari A; European paediatric Soft tissue sarcoma Study Group. Vinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2019 Nov;20(11):1566-1575. Epub 2019 Sep 24. link to original article EuroPMC
##Update: Bisogno G, Minard-Colin V, Zanetti I, Ferrari A, Gallego S, Dávila Fajardo R, Mandeville H, Kelsey A, Alaggio R, Orbach D, Terwisscha van Scheltinga S, Guillén Burrieza G, Ben-Arush M, Glosli H, Mudry P, Ferman S, Devalck C, Defachelles AS, Merks JHM, Jenney M. Nonmetastatic Rhabdomyosarcoma in Children and Adolescents: Overall Results of the European Pediatric Soft Tissue Sarcoma Study Group RMS2005 Study. J Clin Oncol. 2023 May 1;41(13):2342-2349. Epub 2023 Feb 27. link to original article EuroPMC
==VIE==
VIE: Vincristine, Ifosfamide, Etoposide
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Crist et al. 2001 (IRS-IV)	1991-1997 	Phase 3 (E-switch-ic)	1. VAC 	Did not meet co-primary endpoints of FFS/OS
Crist et al. 2001 (IRS-IV)	1991-1997 	Phase 3 (E-switch-ic)	2. VAI 	Did not meet co-primary endpoints of FFS/OS
====Chemotherapy====
*Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15
*Ifosfamide (Ifex) 1800 mg/m2 IV once per day on days 1 to 5
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 5
====Supportive therapy====
*Mesna (Mesnex) (dose/schedule not specified) given with ifosfamide
21-day cycle for 3 cycles
====Subsequent treatment====
*VI & RT consolidation, then VIE consolidation x 1, then VIE continuation
===References===
# IRS-IV: Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, Breneman J, Qualman SJ, Wiener E, Wharam M, Lobe T, Webber B, Maurer HM, Donaldson SS. Intergroup Rhabdomyosarcoma Study-IV: results for patients with nonmetastatic disease. J Clin Oncol. 2001 Jun 15;19(12):3091-102. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
Category:Rhabdomyosarcoma regimens
Category:Disease-specific pages
Category:Soft tissue sarcomas