Treatment of metastatic Ewing sarcoma/primitive neuroectodermal tumor of bone: Evaluation of increasing the dose intensity of chemotherapy-a report from the Children's Oncology Group

• Published in: Pediatric Blood & Cancer Vol. 49; no. 7; pp. 894 - 900
• Main Authors: Miser, James S., Goldsby, Robert E., Chen, Zhengjia, Krailo, Mark D., Tarbell, Nancy J., Link, Michael P., Fryer, Christopher J.H., Pritchard, Douglas J., Gebhardt, Mark C., Dickman, Paul S., Perlman, Elizabeth J., Meyers, Paul A., Donaldson, Sarah S., Moore, Sheila G., Rausen, Aaron R., Vietti, Teresa J., Grier, Holcombe E.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-12-2007
• Subjects: Adolescent; Adult; alkylating agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Bone Neoplasms - diagnosis; Bone Neoplasms - therapy; bone tumors; Child; Child, Preschool; Critical Care; dose intensity; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Infant; Injections, Subcutaneous; Male; metastatic ewing sarcoma; metastatic PNET; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - therapy; Neoplasms, Second Primary - chemically induced; Neoplasms, Second Primary - diagnosis; Neuroectodermal Tumors, Primitive - diagnosis; Neuroectodermal Tumors, Primitive - secondary; Neuroectodermal Tumors, Primitive - therapy; oxazaphosphorine chemotherapy; Risk Factors; Sarcoma, Ewing - diagnosis; Sarcoma, Ewing - secondary; Sarcoma, Ewing - therapy; Survival Rate; Treatment Outcome
• ISSN: 1545-5009; 1545-5017; 1096-911X
• DOI: 10.1002/pbc.21233

Background
The outcome for patients with Ewing sarcoma family of tumors (ESFTs) of bone with metastases at diagnosis remains poor despite new approaches to treatment. We evaluated whether a dose‐intensity chemotherapy regimen improved survival for patients with ESFTs of bone with metastases at diagnosis.
Methods
We entered 60 patients with metastatic ESFTs of bone onto a single arm trial of a new intensive therapy. Treatment consisted of 51‐weeks of chemotherapy and local control of the primary with radiation, surgery, or both. The chemotherapeutic protocol included two alternating blocks: one with vincristine (2 mg/m2), doxorubicin (90 mg/m2), and cyclophosphamide (2,200 mg/m2); and the second with ifosfamide (2,800 mg/m2/day × 5 days) and etoposide (100 mg/m2/day × 5 days).
Results
Of the 60 patients with metastatic ESFTs of bone enrolled onto this single arm trial, 12 had metastasis to lung only, 7 to bone marrow or bone only, 38 to multiple sites, 2 in other sites and 3 not specified. There were three toxic deaths. Six patients (6‐year cumulative incidence: 9%) developed second malignant neoplasms and died. The 6‐year overall event‐free survival (EFS) was 28% (standard error (SE) 6%) and survival (S) was 29% (SE 6%).
Conclusion
An intensified treatment regimen using higher doses of cyclophosphamide, ifosfamide, and doxorubicin increased toxicity and risk of second malignancy without improving EFS and S. Pediatr Blood Cancer 2007;49:894–900. © 2007 Wiley‐Liss, Inc.