NCI grant supports Jefferson trial to study test for colorectal cancer recurrence


Researchers at Jefferson Medical College and the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia are determining if a new test is more accurate than current methods in finding early recurrence of advanced colorectal cancer.

If they're right, they could change the face of colorectal cancer treatment.

Armed with a new five-year, $5.6 million grant from the National Cancer Institute, Scott Waldman, M.D., Ph.D., Samuel M.V. Hamilton Family Professor of Medicine and director of the Division of Clinical Pharmacology at Jefferson Medical College of Thomas Jefferson University, is leading a clinical trial of more than 2,000 patients with colorectal cancer to see if a blood test based on detecting the protein that causes traveler's diarrhea is a better early detection system than current methods.

Finding disease that has returned after treatment is key, says Dr. Waldman, to long-term survival. After initial treatment, patients periodically return to their physicians for checkups to look for recurrent cancer. If a cancer can be caught early, it stands a better chance of being removed. According to Dr. Waldman, as many as 25 percent of such patients may have isolated and potentially removable metastatic disease. Colon cancer is the second leading cause of cancer-related deaths in the United States.

But current surveillance methods have not been very successful in identifying recurring cancer at an early enough stage, Dr. Waldman says, and particularly in identifying isolated cancers that have spread to other areas of the body. The currently used protein marker, CEA, is inadequate because many colon cancers don't make CEA, and typically, it starts to increase in the blood after the cancer has grown to the point that little can be done for the individual.

"We think there is a better way to do this," says Dr. Waldman. Dr. Waldman's test looks for evidence of a protein, guanylyl cyclase C, or GCC, which is expressed only by intestinal cells and outside of the intestine in colon cancers, including cells circulating in the bloodstream. Most colorectal cancers originate in the cells that line the intestine that normally make GCC. When cells become cancerous, they continue to make GCC.

Dr. Waldman and his co-workers couple GCC with a very sensitive detection technology called RT-PCR analysis. RT-PCR can identify one cancer cell in 1 million to 10 million cancer cells.

"If you take a patient blood sample, the blood can be analyzed by RT-PCR and potentially that may be such a sensitive technique that it becomes the earliest detector of recurrent disease," he says. "We're hoping that it is an early detection system for recurrence and that we discover the recurrence at an early enough stage that we can make a clinical impact on the patient. The patient will either be particularly amenable to chemotherapy and we can put the tumor into remission, or we find the isolated metastasis at an early enough stage that it is removable by surgery."

In a previous NCI-supported trial, the researchers showed that GCC testing was an effective tool in determining the extent of disease and diagnosis particularly whether or not it had spread to the lymph nodes. In the current clinical trial, Dr. Waldman is trying to determine if detecting GCC by RT-PCR analysis is a more sensitive and specific way to find recurrent disease earlier than by current standard testing methods.

Each patient will be evaluated by RT-PCR. "The patient and the doctor will be blinded to the results this will not be used to manage the patient," he explains. "We are only trying to determine if this is a marker of early recurrence.

"At the end of the day, we hope everyone who develops recurrent disease was positive by GCC," he says. At the same time, "We'd like to find out if everyone who doesn't develop recurrence is negative by GCC. For those who develop recurrence and are positive by GCC, the GCC is positive earlier than anything else in their monitoring.

"If that's so, then the next study will entail using GCC RT-PCR blood test as a way to monitor patients," he says. "Then, we would treat based on the results." The study is being conducted at several centers, including Thomas Jefferson University Hospital and Fox Chase Cancer Center.

"I'm not sure whether or not it will be earlier than every other test out there," Dr. Waldman says. "This is such a sensitive detection system that it potentially will outperform all other systems."

Dr. Waldman notes that GCC testing may ultimately become part of an integrated surveillance program that would include CEA and chest x-ray.

Source: Eurekalert & others

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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