The IVADo regimen—A pilot study with ifosfamide, vincristine, actinomycin D, and doxorubicin in children with metastatic soft tissue sarcoma

Abstract

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. Cancer 2005. © 2005 American Cancer Society.

Triptolide is an inhibitor of RNA polymerase I and II–dependent transcription leading predominantly to down-regulation of short-lived mRNA

“…Actinomycin D has shown antitumor properties in clinical trials including patients harboring various tumors such as kidney cancers and rhabdomyosarcomas (42,43). This strongly suggests that targeting transcription is a valuable anticancer approach.…”

Sequential intensified chemotherapy with stem cell rescue for children and adolescents with desmoplastic small round-cell tumor

“…Details of this pilot study have already been published. 10 Definition of response and statistics A formal assessment of the primary tumor and all sites of metastases had to be performed after the induction (ninth week) and SICT phases, as well as at the end of the whole treatment. The response criteria used were as follows: complete response (CR) ¼ resolution of all evidence of disease; partial response (PR) ¼ a tumor volume reduction of more than 66%, minor partial response (minor PR) ¼ a tumor volume reduction of less than 66%, but more than 33%; heterogeneous response (HR) ¼ PR at one or more sites but less than PR at other sites, with no progressive disease (PD); a reduction in volume of less than 33% was recorded as stable disease (SD).…”

Selecting multimodal therapy for rhabdomyosarcoma

“…An Italian pilot study was conducted on 29 patients with metastatic soft-tissue sarcomas (19 with RMS) who were given four up-front cycles of ifosfamide, vincristine, actino mycin D and doxorubicin (IVADo) chemotherapy, that is, the well-established standard IVA regimen plus full-dose doxorubicin. The study recorded a response rate of 84% in RMS patients and a generally manageable toxicity (although 67% of cycles were complicated by grade-4 neutropenia) [111]. These results led to the anthracycline question being explored in the new EpSSG randomized trial on localized RMS, in which highrisk patients are randomized to receive IVA (the standard regimen) or IVADo chemotherapy in their first four cycles [27].…”