The IVADo regimen - A pilot study with ifosfamide, vincristine, actinomycin D, and doxorubicin in children with metastatic soft tissue sarcoma: A pilot study on behalf of the European pediatric soft tissue sarcoma study group

BACKGROUND. The role of doxorubicin (Doxo) as part of multidrug regimens used to treat children with soft tissue sarcoma (STS) is controversial. To evaluate the feasibility of combining Doxo with the well established ifosfamide, vincristine, and actinomycin D (IVA) regimen, the Italian STS Committee performed a pilot study on a series of children with metastatic STS. METHODS. Between July 2002 and February 2004, 29 evaluable patients were enrolled in this study; 19 patients had rhabdomyosarcoma, 5 patients had peripheral neuroectodermal tumor, and 5 patients had other types of STS. The IVA-Doxo (IVADo) regimen included ifosfamide 3 g/m² on Days 1 and 2, vincristine 1.5 mg/m² on Day 1, actinomycin D 1.5 mg/m² on Day 1, and Doxo 30 mg/m² on Days 1 and 2. Three courses of IVADo were to be administered in the initial part of treatment and analyzed for toxicity and tumor response. RESULTS. Overall, 92 cycles were delivered. Major regimen-related toxicity was myelosuppression, with Grade 4 neutropenia in 67% of cycles and fever and neutropenia in 37% of cycles. Nonhematologic toxicity included Grade 3-4 mucositis (6.5% of cycles), constipation (9.7%), and peripheral neuropathy (6.5%). Other manifestations of major toxicity were venoocclusive disease and seizures, which occurred in one patient each. All but 1 patient with a malignant schwannoma showed some degree of tumor volume reduction; however, considering only complete and partial remissions, the response rate was 76% (± 7.9%). CONCLUSIONS. The intensive IVADo regimen was effective against pediatric STS with acceptable toxicity. This combination will be investigated in high-risk patients with rhabdomyosarcoma in a randomized trial launched by the European pediatric Soft tissue sarcoma Study Group.