Malempati S, et al. - Researchers reported results from the subsequent Children’s Oncology Group (COG) study (ARST0431) for patients with metastatic rhabdomyosarcoma (RMS), which evaluated the feasibility and efficacy of adding cixutumumab (insulin-like growth factor-1 monoclonal antibody) or temozolomide to the ARST0431 intensive chemotherapy backbone. The two nonrandomized pilot studies initially determined feasibility in patients with metastatic RMS and were expanded to assess efficacy. Fifty-four weeks of chemotherapy, including vincristine/irinotecan, interval-compressed vincristine/doxorubicin/cyclophosphamide alternating with ifosfamide/etoposide, and vincristine/dactinomycin/cyclophosphamide was administered to all the patients. In pilot 1, intravenous cixutumumab (3, 6, or 9 mg/kg) once weekly was administered to patients throughout therapy. In pilot 2, oral temozolomide (100 mg/m²) daily for 5 days with irinotecan was given to patients. Radiation to the primary tumor and to metastatic sites was administered to all patients. Outcomes suggest that for metastatic RMS, the addition of cixutumumab or temozolomide to intensive multiagent chemotherapy was safe and feasible. The improved outcome was not evident with either of the agent when compared with the same chemotherapy that was used on ARST0431.