A Conversation with Dr. Mason Bond on Improving the Treatment of Patients with Ewing Sarcoma
Dr. Mason Bond of the Department of Pediatrics at the University of British Columbia in Vancouver serves as the principal investigator of a Children's Oncology Group (COG) clinical trial. The phase III trial, which is still recruiting patients, is testing the addition of a novel drug combination to standard therapy in patients younger than 50 years who have localized Ewing sarcoma.
How is your treatment trial different from earlier trials?
The basic structure of the trial is similar to that of past trials, but we are testing the addition of vincristine, cyclophosphamide, and topotecan to the standard drug combinations for first-line treatment. In phase II studies, patients with metastatic and relapsed disease showed better responses to this combination than to any other combination recently tested. Since the topoisomerase I inhibitors, like topotecan, are not part of the current standard combinations, we hope that adding a combination that works in a slightly different way can improve progression-free survival. Patients can also receive this experimental combination as an outpatient therapy, which makes it easier for patients to get treated.
We have also modified the definitions of surgical margins, for example, to clarify how far a lesion can be from a margin, and we've incorporated up-to-date radiation oncology techniques. We are looking at other prognostic factors and studying whether PET imaging might help predict either tumor response or patient outcome.
Is this trial only for pediatric patients?
No, this is the first COG trial to enroll young adults through the Clinical Trials Support Unit. Nearly 20 percent of the people in the trial are 18 years or older, but all of them have been enrolled through pediatric centers.
I would like more young adults to participate in this trial. One goal of the pediatric oncology cooperative groups is to encourage older adolescents and young adults to get into clinical trials in any way we can. We have seen with pediatrics how participation in clinical trials leads to improvements in outcomes; young adult participation in clinical trials is the best and fastest way to make improvements for this age group.
How have treatments for Ewing sarcoma been changing?
The treatment changes, in general, have been a little slow. We were quite excited when a trial published in 2009 showed that treatment given every 2 weeks yielded better results than treatment given every 3 weeks, because other ways of intensifying treatment that we tested had not produced better results. The last time there was a big step forward like this was in 2003, with the addition of ifosfamide and etoposide.
Since then, we have been looking for new agents to add to first-line treatment that would improve progression-free survival. There has been a lot of effort looking for new biologic agents, but we have not been able to identify one to test in Ewing sarcoma just yet. The best chemotherapy combination for which there is quite a lot of information in phase II trials, and in patients with relapsed, refractory, and metastatic disease, was cyclophosphamide and topotecan. That is why we decided to test that combination in our study.
Researchers are still hoping to identify more specific agents for Ewing sarcoma, such as new agents that target signaling pathways. It just takes a long time for agents to be tested in pediatric populations and for agents with an adult indication to be identified for use in pediatric patients. I think the identification of new and effective agents to test in [early-phase] trials is the key to moving treatment forward.
Are there certain patients who still have a poorer prognosis?
People who have metastatic disease at the time of diagnosis have poor outcomes. Trying to find an effective treatment for them, and even trials for them, has been challenging, but they are also the people who are more likely to be part of clinical trials testing new agents at an earlier stage.
In general, older adolescents and young adults also have a poorer prognosis than younger people, and one of the challenges has been enrolling young adults in trials. It is important to capture older adolescents and young adults in these kinds of trials, because enrolling them in trials could improve progression-free survival in that age group in a way that has not really happened in recent years.
NCI Cancer Bulletin for November 29, 2011 - National Cancer Institute