Previously Untreated Childhood Rhabdomyosarcoma
- High-dose chemotherapy with stem cell rescue has been evaluated in a limited number of patients with rhabdomyosarcoma.; [Level of evidence: 3iiiA] The use of high-dose chemotherapy with stem cell rescue has failed to improve the outcome of patients with newly diagnosed or recurrent rhabdomyosarcoma.
Treatment options under clinical evaluation
The following are examples of national and/or institutional clinical trials that are currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.
- COG-ARST08P1: COG-ARST08P1 evaluates the addition of novel therapeutic agents to the intensive chemotherapy used in the COG study COG-ARST0431. Newly diagnosed patients with metastatic rhabdomyosarcoma (excluding patients younger than 10 years with embryonal rhabdomyosarcoma) who have an expected failure-free survival of less than 20% are eligible. The study consists of the following three sequential pilots:
- Pilot 1 assesses the feasibility of adding IMC-A12, a fully human IgG1 monoclonal antibody targeting the insulin-like growth factor-I receptor (IGF-IR), to most known effective chemotherapy agents in rhabdomyosarcoma.
- Pilot 2 assesses the feasibility of adding temozolomide, an alkylating agent, to vincristine/irinotecan cycles, based on the synergistic activity of temozolomide when added to irinotecan.
- Pilot 3 will assess the feasibility of adding both agents to the COG-ARST0431 backbone, provided that pilot studies 1 and 2 have not shown unexpected toxicity.
- The NCI's intramural Pediatric Oncology Branch is conducting a study of consolidative immunotherapy incorporating T-cell reconstitution followed by a dendritic-cell plus tumor-peptide vaccine that could be given with little toxicity to patients with translocation-positive metastatic or recurrent Ewing sarcoma and alveolar rhabdomyosarcoma.[Level of evidence: 3iiiA]
Radiation Therapy Management Options
RT is an effective method for achieving local control of tumor for patients with microscopic or gross residual disease following biopsy, initial surgical resection, or chemotherapy. Patients with completely resected tumors (Group I) of embryonal histology do well without RT,[60,61] but RT benefits patients with Group I tumors with alveolar or undifferentiated histology. A review of European trials conducted by the Cooperative Soft Tissue Sarcoma Study Group between 1981 and 1998 in which RT was omitted for some Group II patients demonstrated a benefit to using RT as a component of local tumor control for all Group II patient subsets (defined by tumor histology, tumor size, and tumor site). Local failure is the predominant type of relapse for patients with Group III disease. Patients with tumor-involved regional lymph nodes at diagnosis have a higher risk of local and distant failure compared with patients whose lymph nodes are negative. As with the surgical management of patients with rhabdomyosarcoma, recommendations for RT depend on the site of primary tumor and on the amount of residual disease, if any, following surgical resection. For patients with head and neck rhabdomyosarcoma, four studies reported excellent local control in patients treated with intensity-modulated radiation therapy (IMRT) or fractionated stereotactic radiation therapy and chemotherapy over a 4-year period. Further study is needed, but the use of IMRT and chemotherapy in patients with head and neck rhabdomyosarcoma may result in less severe late effects.[91,92,93,94]; [Level of evidence: 3iiiA]