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Intensified chemotherapy regimen failed to improve outcomes in high-risk rhabdomyosarcoma
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Patients with non-metastatic rhabdomyosarcoma received no survival advantage or reduction in intensity of local therapy when treated with an intensified regimen of chemotherapy, and they were exposed to increased rates of toxicity, according to the results of the International Society of Pediatric Oncology’s MMY95 study.
“Overall survival rates for patients with localized rhabdomyosarcoma now exceed 70% and, for some groups of patients with favorable disease, may exceed 90%, but outcome for less-favorable disease remains unsatisfactory,” the researchers wrote.
The MMT95 study was designed to test an intensified chemotherapy strategy in a group of children with high-risk rhabdomyosarcoma.
The researchers enrolled 457 children aged 6 months to 18 years with incompletely resected embryonal rhabdomyosarcoma, undifferentiated sarcoma or soft tissue primitive neuroectodermal tumors.
All patients were randomly assigned to treatment with ifosfamide, vincristine and dactinomycin (IVA) with carboplatin, epirubicin and etoposide (n=224), or IVA alone (n=233).
If no response was seen with IVA alone after three courses, patients were allowed to switch to the six-drug regimen.
OS for the entire patient population was 81%, with 174 treatment failures and 131 deaths. No difference in OS was observed between treatment groups (82% for IVA alone vs. 80% for the six-drug arm), or event-free survival. Data indicated that those patients who had genitourinary, orbital or nonparameningeal head and neck tumors had better survival than other patients (P<.01).
Those patients assigned to the six-drug combination reported more leucopenia, thrombocytopenia, stomatitis, anemia, neutropenia and fever than patients assigned to IVA alone (P<.01).
“Despite broadening chemotherapy exposure with a six-drug combination, this study did not find a difference in outcome compared with patients treated with IVA alone, and there was a statistically significant increase in toxicity,” the researchers wrote.
For more information:
- Oberlin O. J Clin Oncol. 2012;doi:10.1200/JCO.2011.40.3287.
Perspective
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Holly L. Spraker-Perlman, MD, MS
As the researchers state, it is difficult to compare the results of this trial to those from the Soft Tissue Sarcoma Committee of the Children’s Oncology Group (COG) as the risk stratification used is different. The population eligible for the SIOP MMT95 study and called “high-risk nonmetastatic” could be included in the low- or intermediate-risk rhabdomyosarcoma categories by the current COG Soft-Tissue Sarcoma Committee definitions (Malempati S. Pediatr Blood Cancer. 2012;59:5-10) depending on the histology and the extent of resection of the tumor. These three risk groups would then be treated on different protocols, with varying schedules and medications. Still, other patients enrolled on this trial would be treated on COG protocols for either soft-tissue sarcoma (undifferentiated sarcomas – ARST0332) or Ewing sarcoma (those patients with PNET – AEWS1031). The overall findings show that in these patients, the addition of three agents — carboplatin, epirubicin and etoposide — to a backbone of ifosfamide, vincristine and dactinomycin did not increase event-free survival or OS, yet it did increase the toxicity of therapy. For this reason, the six-drug combination should no longer be used for these patients. Although the nomenclature varies between SIOP and COG, both groups are dedicated to stratifying patients by risk of recurrence. This will allow patients who are at a lower risk of relapse a reduction in therapy, and attempt to prevent late effects of chemotherapy. For patients with metastatic or recurrent disease, escalation of therapy with newer agents or combinations of agents will continue in randomized trials in order to pursue a cure.
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