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Intensive, multi-agent regimen may prolong EFS in metastatic rhabdomyosarcoma
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Pediatric and young adult patients with metastatic rhabdomyosarcoma who had no more than one Oberlin risk factor experienced favorable EFS outcomes with intensive multi-agent therapy, according to study results from the Children’s Oncology Group.
However, patients with two or more Oberlin risk factors experienced a poor prognosis even with the combined-therapy regimen, which included dose-compressed chemotherapy and radiation, results showed.
“Although improvements in treatment strategies for patients with localized rhabdomyosarcoma have occurred over the past 3 decades by decreasing toxicity without compromising cure, little progress has been made in curing patients with metastatic disease,” Carola A.S. Arndt, MD, professor of pediatrics and adolescent medicine at Mayo Clinic in Rochester, Minn., and colleagues wrote. “Patients with stage IV disease, with the exception of those younger than 10 years who have embryonal rhabdomyosarcoma, have long-term EFS of less than 20%.”
Arndt and colleagues from the Children’s Oncology Group sought to observe whether multi-agent therapy would improve outcomes among 109 patients (55% male) with metastatic rhabdomyosarcoma. The majority of patients were aged 10 years or older (10-20 years, n = 61; ≥ 21 years, n = 7).
Researchers used three strategies to improve outcomes in this population: the use of dose intensity by interval compression, selection of the most active agents evaluated in phase 2 window studies and use of irinotecan as a radiation sensitizer.
Patients received 54 weeks of therapy comprised of blocks of vincristine and irinotecan (weeks 1-6, 20-25 and 47-52); interval compression with vincristine, doxorubicin and cyclophosphamide, alternating with etoposide and ifosfamide (weeks 7-19 and 26-34); and vincristine, dactinomycin and cyclophosphamide (weeks 38-46).
Patients underwent primary radiation therapy weeks 20 to 25. Radiation therapy also was permitted at weeks 1 through 6 for intracranial or paraspinal extension, and weeks 47 through 52 for extensive metastatic sites.
Median follow-up for surviving patients was 3.8 years (range, 7.7 months to 4.7 years).
In the overall cohort, the 3-year EFS rate was 38% (95% CI, 29-48) and the 3-year OS rate was 56% (95% CI, 46-66).
The researchers then stratified patients based on Oberlin risk factors — including age older than 10 years or younger than 1 year, unfavorable primary disease site, three or more metastatic sites, and bone or bone marrow involvement — to analyze EFS.
Among high-risk patients with zero to one Oberlin risk factors, 69% (95% CI, 52-82) achieved 3-year EFS. In contrast, patients with two or more Oberlin risk factors had a 3-year EFS rate of 20% (95% CI, 11-30).
When researchers compared data from the overall population with historical data from a cohort of similar patients with metastatic rhabdomyosarcoma treated on the Intergroup Rhabdomyosarcoma Study-IV pilot trial — which evaluated ifosfamide/doxorubicin- and ifosfamide/etoposide-based regimens — patients in the current analysis appeared to achieve significantly prolonged median EFS (2.11 months vs. 1.44 months; P = .0477).
The researchers observed toxicity profiles similar to those seen in previous studies. Twenty-five patients never received radiation therapy due to withdrawal from protocol (n = 11), progressive disease (n = 6), loss to follow-up (n = 1) or completion of all therapy without radiation (n = 7).
“These approaches will be explored in future studies in high-risk rhabdomyosarcoma,” Arndt and colleagues wrote. – by Cameron Kelsall
Disclosure: Arndt reports ownership interests in Merck and Pfizer. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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