Rhabdomyosarcoma
Section editor | |
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Elizabeth J. Davis, MD Vanderbilt University Nashville, TN, USA |
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:
5 regimens on this page
5 variants on this page
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Guidelines
NCCN
- NCCN does not have guidelines at this granular level; please see NCCN Guidelines - Soft Tissue Sarcoma.
All lines of 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.
Chemotherapy
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 PubMed
- 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 PubMed
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 |
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 |
References
- IRS-I: 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 PubMed
- 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 PubMed
- 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 PubMed
- 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 PubMed 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 PubMed 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 |
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, then IVA | Did not meet primary endpoint of EFS36 |
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 PubMed
- 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 PubMed 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 PubMed 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 PubMed
VI, then VDC/IE, then VAC, then VI
VI, then VDC/IE, then VAC, then VI: Vincristine & Irinotecan, followed by Vincristine, Doxorubicin, Cyclophosphamide alternating with Ifosfamide & Etoposide, followed by Vincristine, Actinomycin D, Cyclophosphamide, followed by Vincristine & Irinotecan
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Weigel et al. 2015 (COG ARST0431) | 2006-2008 | Phase 2 |
Note: this is a complicated 54-week protocol with no immediate plans to add details to HemOnc.org. Please refer to the original article.
Chemotherapy, VI portion
Chemotherapy, VDC portion
Chemotherapy, IE portion
Chemotherapy, VAC portion
References
- COG ARST0431: Weigel BJ, Lyden E, Anderson JR, Meyer WH, Parham DM, Rodeberg DA, Michalski JM, Hawkins DS, Arndt CA. Intensive Multiagent Therapy, Including Dose-Compressed Cycles of Ifosfamide/Etoposide and Vincristine/Doxorubicin/Cyclophosphamide, Irinotecan, and Radiation, in Patients with High-Risk Rhabdomyosarcoma: A Report from the Children's Oncology Group. J Clin Oncol. 2016 Jan 10;34(2):117-22. Epub 2015 Oct 26. link to original article link to PMC article PubMed NCT00354744
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 |
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
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 contains dosing details in manuscript PubMed