Very intensive, short-term chemotherapy for children and adolescents with metastatic sarcomas.

Background: To improve the prognosis for pediatric patients with metastatic sarcomas, including the Ewing sarcoma family of tumors (ESFT), rhabdomyosarcoma (RMS), and undifferentiated sarcoma (UDS), we tested the feasibility of a brief, intensive regimen of chemotherapy that maximizes dose intensity.

Procedure: Twenty-four children and adolescents with metastatic sarcomas received VACIME chemotherapy, consisting of eight courses of vincristine 2 mg/m(2) on day 0; doxorubicin 20 mg/m(2)/day on days 0-3; cyclophosphamide 360 mg/m(2)/day on days 0-4; ifosfamide 1,800 mg/m(2)/day on days 0-4; mesna 2,400 mg/m(2)/day; and etoposide 100 mg/m(2)/day on days 0-4. Doxorubicin was omitted in courses 7 and 8. Granulocyte colony-stimulating factor (G-CSF) was used routinely following each course of therapy. Courses of therapy were repeated every 21 days or as soon as hematopoietic recovery and resolution of nonhematopoietic toxicities permitted. Surgical resection followed course 6, and radiotherapy followed the completion of all therapy.

Results: Thirteen patients achieved a complete response (CR) with chemotherapy alone, and seven more achieved a CR following surgical resection after course 6 (overall CR rate 83%). There was one toxic death. Thirteen patients developed progressive disease, with 2- and 4-year event-free survivals (95% confidence interval) of 50% (30-70%) and 45% (25-65%), respectively. Myelosuppression was severe and cumulative, leading to dose reductions and chemotherapy interval delays. Mucositis was the most common nonhematopoietic toxicity.

Conclusions: VACIME chemotherapy was a feasible dose-intensive regimen for pediatric patients with metastatic sarcomas. Cumulative hematopoietic toxicity and severe mucositis limited the delivery of chemotherapy as prescribed. The CR and 2-year event-free survival rates were superior to those of most previously reported regimens.