Cancer Health Center

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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-ARST0531: The COG intermediate-risk rhabdomyosarcoma protocol is comparing standard VAC chemotherapy versus VAC alternating with vincristine and irinotecan (VI). RT begins at week 4 in conjunction with VI to determine the potential benefit of early local therapy in this group of patients.

High-risk patients

Standard treatment options

• High-risk patients have metastatic disease in one or more sites at diagnosis (stage IV). These patients continue to have a relatively poor prognosis (5-year survival rate of 50% or lower) with current therapy, and new approaches to treatment are needed to improve survival in this group.[62,77,78]

  In a pooled analysis of high-risk rhabdomyosarcoma patients treated with multiagent chemotherapy (all chemotherapy regimens used a cyclophosphamide or ifosfamide plus dactinomycin and vincristine-based backbone with variation as to the use of additional chemotherapy agents) followed by local therapy (surgery with or without RT) within 3 to 5 months of starting chemotherapy, adverse prognostic factors in patients presenting with metastatic disease included: age younger than 1 year or age 10 years or older, unfavorable primary site, bone and/or bone marrow involvement, and three or more metastatic sites. The event-free survival (EFS) rate at 3 years was 50% for patients without any of these adverse prognostic factors. The EFS rates were 42% for patients with one adverse prognostic factor, 18% for patients with two adverse prognostic factors, 12% for patients three adverse prognostic factors, and 5% for patients with four adverse prognostic factors.[79][Level of evidence: 3iiiA]

  The standard systemic therapy for children with metastatic rhabdomyosarcoma is the three-drug combination of VAC. Despite many clinical trials attempting to improve outcome by adding additional agents to standard VAC chemotherapy (or substituting new agents for one or more components of VAC chemotherapy), to date, no chemotherapy regimens have been shown to be more effective than VAC, including the following:

  • In the IRS-IV-STAGE-1 study, three combinations of drug pairs were studied in an up-front window: IE, vincristine/melphalan (VM),[80] and ifosfamide/doxorubicin (ID).[81] These patients received VAC after the up-front window agents were evaluated at weeks 6 and 12. OS for patients treated with IE and ID was comparable (31% and 34%, respectively) and better than those treated with VM (22%).[81] However, results with VAC chemotherapy for stage IV rhabdomyosarcoma in the North American experience are similar.
  • Results from a phase II window trial of patients with metastatic disease at presentation and treated with topotecan and cyclophosphamide showed activity for this two-drug combination, but survival was not different from that seen with previous regimens.[72,73] An up-front window trial of topotecan in previously untreated children and adolescents with metastatic rhabdomyosarcoma gave similar results.[71]
  • Irinotecan and irinotecan with vincristine [82] have also been evaluated as up-front windows by the COG-STS; the response rates were better when irinotecan was administered with vincristine than without it, but again, survival in a preliminary analysis was not improved over prior experience.[82]
  • In a French study, 20 patients with metastatic disease at diagnosis received window therapy with doxorubicin for two courses. Thirteen of 20 patients responded to therapy, and four patients had progressive disease.[83]
  • A study from the International Society of Pediatric Oncology (SIOP) demonstrated continued poor outcome for patients with high-risk features such as age 10 years and older or bone/bone marrow involvement. This study compared a standard six-drug combination followed by vincristine, doxorubicin, cyclophosphamide (VAC) maintenance versus an arm that evaluated a window of single-agent doxorubicin or carboplatin followed by sequential high-dose monotherapy courses including cyclosphosphamide, etoposide, and carboplatin followed by maintenance VAC. No benefit was seen for the high-dose therapy arm.[84]