MMT 95 Study For Rhabdomyosarcoma and Other Malignant Soft Tissue Tumors of Childhood

OBJECTIVES:

• Assess whether good survival rates can be maintained for patients with stage I (pathologic T1) soft tissue sarcomas (STS) treated with limited chemotherapy after complete surgical resection, and whether disease-free survival can be improved by improving the precision of pretreatment staging and the assessment of the completeness of the resection.
• Compare the survival of patients with high-risk nonmetastatic STS treated with alternating regimens of carboplatin, epirubicin, and vincristine (CEV) and ifosfamide, vincristine, and etoposide (IVE) vs continuation of ifosfamide, vincristine, and dactinomycin (IVA) after initial therapy with IVA.
• Assess whether the improved outcome seen for patients with stage III (node positive) STS in an earlier protocol (SIOP-MMT-89) can be maintained with 3 courses of alternating CEV/IVE without altering local therapy.
• Compare outcome of patients with nonmetastatic STS to those with stage IV STS who are registered on this protocol but referred to treatment on the European Intergroup Stage IV Study.
• Assess survival and the risk of late sequelae in patients with non-rhabdomyosarcoma malignant mesenchymal tumors treated on this protocol.
• Evaluate the role of neoadjuvant chemotherapy, new prognostic factors (e.g., ploidy, histologic grading), and recommendations for the management of fibrosarcoma in infants and of fibromatoses.
• Assess ifosfamide nephrotoxicity based on total dose administered and the long-term toxicity based on the potential predictive value of early evidence of nephrotoxicity.

OUTLINE: This is a randomized study for patients with high-risk, nonmetastatic sarcoma, except those with the following characteristics: age less than 6 months, stage I/II non-alveolar orbital tumor, stage III disease, or age less than 3 years with parameningeal disease. Patients are stratified according to disease type (rhabdomyosarcoma (RMS) vs non-RMS disease), parameningeal site of disease, and participating center. Patients with RMS are further randomized by alveolar histology. Randomization occurs after the first course of chemotherapy.

All patients, regardless of disease stage, are registered to this study and outcome is followed, although patients with metastatic RMS or non-RMS malignant mesenchymal tumors are referred for treatment on the SIOP-MMT-98 study. Patients diagnosed more than 8 weeks prior to entry or who are unavailable for follow-up are not treated on study. Doses are modified for patients under 1 year of age or under 10 kg of body weight. All other patients are assigned therapy based on risk group.

After surgery, patients with complete resection and with proven or possible chemosensitive histologies proceed to chemotherapy on the low-risk regimen. Patients with questionable completeness of resection proceed to chemotherapy for standard-risk or high-risk tumors, as appropriate. Regardless of resection results, patients who underwent scrotal surgery for paratesticular tumors proceed to chemotherapy for standard-risk tumors. Alveolar RMS is considered high risk.