CHAPEL HILL, NC – In a review article published this month in The Oncologist, UNC’s Dr. Richard M. Goldberg and a team of colleagues catalogue how the data collected in a single large comparative clinical trial testing combination chemotherapy for metastatic colorectal cancer has been used not only to benefit the patients that enrolled but also patients who subsequently developed the disease.
It has also helped to refine the clinical trials process and move forward the potential for individualized therapy for patients. These benefits of this collaboration between patients, physicians across the U.S. and Canada, the National Cancer Institutes of the U.S. and Canada, and two pharmaceutical companies (Pharmacia and sanofi-aventis) are being still being realized five years after the original trial concluded.
Not only did the Phase III trial, which ran from 1997-2004, prove that combination chemotherapies adding new drugs to the standard treatment in use for 50 years are effective in treating metastatic colorectal cancer, but it also provided data for more than 25 additional scientific papers. This ongoing research has helped to improve the prognosis and change the standard of care for patients with this diagnosis.
“The history of this study shows how patients’ decisions to enroll in clinical trials can benefit thousands of others, even years down the road,” said Goldberg, who is Physician-in-Chief of the N.C. Cancer Hospital and Associate Director for Clinical Research at UNC Lineberger Comprehensive Cancer Center.
“These individuals have helped doctors and scientists change the way we treat metastatic colorectal cancer and simplify the way we run clinical trials in cancer patients.” Based on the trial the US Food and Drug Administration approved a new agent, oxaliplatin, administered with 5-fluorouracil for the indication "treatment of previously untreated patients with colorectal cancer that had spread to other organs" in 2004.
As one of the first clinical trials to monitor chemotherapy toxicity in real-time, the study allowed researchers to quickly eliminate drug combinations that were more likely to result in negative outcomes for patients. Over the course of the study, as the field of pharmacogenetics evolved, researchers were able to use the individual patients' DNA collected with a simple blood test to better pinpoint which were most likely to have severe side effects. The DNA analysis also helps doctors determine which patients derive greater benefits from a particular drug and adjust their chemotherapy to minimize risk, while maximizing the chances that their cancer would respond to therapy.
“Over time, the fact that this study collected DNA and plasma with patient permission has been important to our ability to make significant progress in understanding how patients’ genetic profiles interact with anti-cancer drugs,” said Goldberg.
Data from the study was also used to examine how patients did with a combination of surgery and drug therapy, to study how the combination drug therapy worked in patients with different risk profiles based on the type and progression of their cancer, and to assess the economic cost-benefit of combination therapies.
"The original data collected has also been combined with data from other clinical trials to examine overall survival rates and to explore differences in outcomes based on patient age and symptom profiles so that we could understand the risks and benefits when we treat older and sicker patients with the more intensive treatments" Goldberg said. "The data was also used to simplify how we follow tumor measurements and side effect profiles in clinical trials speeding the pace and reducing the cost of research."
“The history of this study demonstrates how sharing data among groups of scientists and doctors and asking questions that span scientific disciplines can help us make progress that is meaningful for patients over the relatively short time frame of approximately a decade,” he added.
Other investigators on the review study were Hanna Sanoff, MD, clinical assistant professor of medicine and Howard McLeod, PharmD, professor of pharmacy and UNC Lineberger member, Daniel J. Sargent, PhD, Erin Green and Jan Buckner, MD from the Mayo School of Medicine in Rochester, Minnesota, and Roscoe Morton, MD from the Iowa Oncology Research Association CCOP.
The original clinical trial was a partnership between the enrolled patients, the National Cancer Institutes of the US and Canada, NCI sponsored cooperative groups, industry, and investigators at academic centers, Community Clinical Oncology Programs and private practices. The review study was supported by the North Central Cancer Treatment Group (NCCTG) and NCCTG Biospecimen Resource, sanofi-aventis and Pharmacia.
Contact: Ellen de Graffenreid, 919-962-3405,