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IRS Studies

The overall survival rate for children with rhabdomyosarcoma (RMS) has increased from about 20% to 70% since the 1960s.  Much of this improvement has been due to work done in the Intergroup Rhabdomyosarcoma Studies (IRS). 

Three multidisciplinary cancer treatment groups worked together.  Intergroup Rhabdomyosarcoma Study - I (IRS-I) was opened for patient entry from 1972-78.  IRS-II opened in 1978 and IRS-III in 1984. 

These studies have built on one another and provided a data base of over 1500 patients.

Summary of Results:


  • Clinical Group I patients treated with VAC achieved no additional benefit from local radiation therapy (RT).
  • The addition of cyclophosphamide to VA added no benefit for Group II patients who received irradiation.
  • Doxorubicin did not add benefit to VAC in Group III patients.


  • VA given for 12 or 24 months is equivalent in Group I patients with no local irradiation.
  • Doxorubicin added to VAC does not improve outcomes in Group III or IV patients


  •  Doxorubicin did not add benefit to VAC in Group II patients.
  • The addition of cisplatin, etoposide and doxorubicin to VAC did not show advantage in Group III and IV patients.


  • Substitution of ifosfamide for cyclophosphamide with VA showed no statistical difference
  • Vincristine, ifosfamide and etoposide showed no advantage to VAC.
  • Comparison of vincristine and melphalan to ifosfamide and etoposide showed no difference in response rate in patients with untreated metastatic rhabdomyosarcoma. 
  • Overall survival at 3 years was lower for the vincristine / melphalan group.
  • Granulocyte - Colony Stimulating Factor (G-CSF) is available for use in IRS-IV. 
    • This is a glycoprotein haematopoietic growth factor produced by numerous cell types. 
    • It stimulates the growth of neutrophil precursors and is an activator of mature human granulocytes and significantly decreases the severity and length of chemotherapy induced neutropenia.

Overall and failure free survival has improved with each IRS study, likely due to an overall increase in the cumulative cyclophosphamide dose.

No study has so far shown a benefit for high dose chemotherapy followed by stem cell rescue.



R. Beverly Raney, Harold M. Maurer, James R. Anderson, Richard J. Andrassy, Sarah S. Donaldson, Stephen J. Qualman, Moody D. Wharam, Eugene S. Wiener and William M. Crist







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