CTOS Op Ed

CTOS Op Ed

There is no reason to include age as an entry criterion for any clinical trial

Paul A. Meyers, M.D.

Vice Chair, Department of Pediatrics

Memorial Sloan-Kettering Cancer Center

1275 York Avenue

New York, New York 10021

[Editor's Note: This is the third in the series of Op Ed pieces written by one of the members of the Board of Directors of the Connective Tissue Oncology Society (CTOS). These Op Ed pieces are intended to address important and controversial issues in the field. The “CTOS Questions, Comments & Counterpoint” column allows readers to express their opinions in response to these Op Ed pieces. Click here to send in an opinion.]

Cancer occurs at all ages. Some cancers are more common in young patients, some in older. The site of origin, likelihood of spread to other areas of the body, and predicted outcomes for a specific cancer is much more dependent on the type of cancer than on the age of the patient. Ewing sarcoma behaves in the same manner in a 35 year old patient as it does in a 15 year old patient. Our objective should be to find optimal treatment for every patient and to learn as much as we can about specific cancers to improve those treatments. For many patients, participation in clinical trials provides access to treatment that represents the distillation of the thinking of dozens of experts in that specific cancer. Artificial barriers based on age can obstruct patient access to clinical trials. The issue is not whether adults with “pediatric sarcomas” should be treated on pediatric trials. The issue is that patients should be treated on the best trials available. Some sarcomas are more common in young patients, such as rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma. There is a long and largely successful tradition of clinical trials for these tumors in the pediatric oncology cooperative groups. The pediatric groups have learned to write protocols with no age requirement for eligibility. These trials are universally available to patients of any age. Are they appropriate for every patient? Clearly, the answer is no. Some older patients have other health problems such as heart or kidney disease that preclude administration of the drugs called for in these trials. These legitimate reasons to decline participation are addressed by eligibility requirements for minimal organ function, rather than an arbitrary age cutoff. Is it possible that a “pediatric” sarcoma arising in an adult is different from the same tumor arising in a child? Possibly. The best way to answer the question is to treat these two groups in the same way and look for differences in biological factors or outcomes which can be attributed exclusively to age. This is accomplished if adult patients take part in clinical trials alongside younger patients. This concept has a clear corollary. For sarcomas that are more common in adults, the expertise and the clinical trial experience has largely derived from the internal medicine, or adult cooperative groups. If a child develops a tumor that is more common in adults, we should be able to offer that child participation in a clinical trial appropriate for the diagnosis. Unfortunately, most internal medicine cooperative group trials are written with an age restriction excluding patients less than 18 years old. There is no biological basis for this exclusion and it should be discontinued. Participation of minors in clinical trials requires additional steps to obtain informed consent from the legal guardian and to document assent of the minor. The system we have in place for approval of new drugs in the United States makes a sharp distinction between adults and minors, and has often required a specific trial in children before drugs are allowed to be given to minors. The Sarcoma Alliance for Research through Collaboration (SARC) is a clinical trials group dedicated to seeking better treatments for patients with sarcomas. We have been successful in mounting clinical trials for sarcomas that improve access of all patients to appropriate therapies. We carried out a trial of imatinib for sarcomas other than GIST and we were able to open the trials to all patients 13 and older. We have worked with the FDA to develop new trials in which we have been able to use the same age criteria. Is there a need to test drugs specifically in children? Obviously there is a need for new agents to be tested in children to be sure that they do not negatively impact growth and development, specifically pediatric issues. But many clinical trials involve conventional agents that have already been tested in both age groups. There is no reason to include age as an entry criterion for any clinical trial. We should make the best therapy available to all.