Treatment of Ewing sarcoma family of tumors with a modified P6 protocol in children and adolescents


  • Conflicts of interest: Nothing to declare.



Reported overall survival (OS) rates of patients with localized Ewing sarcoma family of tumors (ESFT) are >80% when treated with the MSKCC P6 protocol. However, it has been associated with a 5.8% incidence of secondary leukemias. A modified P6 (mP6) protocol with reduced exposure to chemotherapy is presented.


Thirty-one newly diagnosed ESFT patients were enrolled onto this phase II, single-arm, non-randomized protocol. Courses 1, 2 and 4 consisted of cyclophosphamide 4.2 g/m2, doxorubicin 75 mg/m2, and vincristine 2 mg/m2 (CDV). Cycles 3 and 5 consisted of ifosfamide 9 g/m2 and etoposide 500 mg/m2 (IE). Course 5 ifosfamide was 14 g/m2 if necrosis was <90%.


Twenty-four patients had loco-regional disease and seven had metastases. The 4-year event-free survival (EFS) rate for patients with localized tumors is 83% and overall survival (OS) is 92%. The 3-year EFS rate for patients with distant metastases is 28% and OS rate is 42%. EWS-FLI1 fusion genes were detected in 17 cases (74%) and EWS-ERG in six cases (26%). Type 1 EWS-FLI1 variant was present in 6/7 metastatic patients and 3/16 loco-regional cases (P = 0.001). None of the patients experienced tumor progression before remission. All relapses occurred within 2 years from the end of treatment and local relapses (n = 3) happened in patients who did not receive radiation therapy. No secondary malignancies have been observed, median follow-up of 4.3 years for surviving patients.


In this pilot study, the mP6 protocol produced a complete remission rate of 83% at 4 years in non-metastatic ESFT reducing the risk of secondary malignancies. Pediatr Blood Cancer 2011;57:69–75. © 2011 Wiley-Liss, Inc.