UC Irvine's Zell leads national trial in colon cancer prevention

Jason A. Zell, DO, MPH, of UCI Health, is leading a nationwide research study to test whether two drugs can help prevent the recurrence of cancers and the development of new adenomas,  or potentially precancerous growths, in patients who have already battled colon cancer. The clinical trial is now open to enrollment.

There are more than 1 million colon cancer survivors in the United States today, and that number is growing. Even after these patients complete treatment and are cancer‐free, their risk of developing precancerous growths or a second cancer is notably higher than the risk faced by the general population.

“We can do more to prevent cancers by targeting groups at greater risk,” said Zell, the study’s principal investigator and a hematologist/oncologist at the UC Irvine Medical Center and Chao Family Comprehensive Cancer Center. “Colon cancer survivors in particular stand to benefit from further risk reduction strategies.”

The Preventing Adenomas of the Colon with Eflornithine and Sulindac (PACES) clinical trial, with support from the National Cancer Institute, will enroll about 1,488 patients who have recently completed treatment for colon cancer. Participants will take either eflornithine, sulindac, both drugs or a placebo  daily for three years and will then have a colonoscopy to check for precancerous polyps, or abnormal growths of tissue also known as adenomas. A placebo is an inactive substance given to some trial participants to test whether the active drug or drugs have a real effect.                                          

“A previous trial found that this combination had substantial preventive effects in patients who had been treated for colorectal adenomas,” said Zell. “PACES should tell us whether those observed benefits also extend to colon cancer survivors.”

In this earlier study, people who had had adenomas removed from their colon who then took daily eflornithine and sulindac for three years lowered their risk of developing another adenoma during the following three years to less than one third of what it was for those who did not take the drugs. More importantly, the adenomas that were most likely to be prevented were the ones that are most likely to become colon cancer; the patients’ chances of developing a high-risk adenoma dropped by 90 percent.

Eflornithine and Sulindac have not been approved by the U.S. Food and Drug Administration specifically for colon cancer prevention. These investigational drugs are being tested. Eflornithine has been used intravenously to treat trypanosomiasis, sometimes called “sleeping sickness,” and in a skin cream to reduce unwanted hair growth.

Sulindac is a non‐steroidal anti‐inflammatory drug (NSAID) used to treat pain caused by arthritis, or a form of joint inflammation . It has been shown to reduce the number of colon polyps in people who have an inherited condition that leads them to develop hundreds or even thousands of such polyps.

Both drugs lower the body’s levels of a group of naturally‐formed molecules called polyamines, though the drugs work in different ways. Excess polyamines have a role in the development of colorectal cancer.

Those who have had surgery for colon cancer within the previous 9 – 15 months, have since completed any chemotherapy, and are now considered cancer‐free may be eligible to take part in the PACES trial.

Colon cancer is the second‐leading cause of cancer death in the U.S. Each year, more than 140,000 new cases are diagnosed and 50,000 people die from it annually, according to NCI statistics.

The PACES study, also known as S0820, is being conducted by SWOG (Leading Cancer Research.

Together), a cancer research cooperative group within the NCI’s National Clinical Trials Network, in collaboration with other NCI cooperative groups.

For information about the PACES trial at the Chao Family Comprehensive Cancer Center, please call toll‐free: 877.UC.STUDY (877.827.8839) or email ucstudy@uci.edu. Please refer to Protocol No. SWOG‐S0820. More details about the study are also online at clinicaltrials.gov/ct2/show/NCT01349881 or at swog.org/patients/paces.

The University of California, Irvine is a member of SWOG, which designs and conducts multidisciplinary clinical trials to improve the practice of medicine in preventing, detecting, and treating cancer, and to enhance the quality of life for cancer survivors.

UCI Health comprises the clinical, medical education and research enterprises of the University of California, Irvine. Patients can access UCI Health at physician offices throughout Orange County and at its main campus, UC Irvine Medical Center in Orange, Calif., a 412-bed acute care hospital that provides tertiary and quaternary care, ambulatory and specialty medical clinics, behavioral health and rehabilitation. U.S. News & World Report has listed it among America’s Best Hospitals for 13 consecutive years. UC Irvine Medical Center features Orange County’s only National Cancer Institute-designated comprehensive cancer center, high-risk perinatal/neonatal program, Level I trauma center and Level II pediatric trauma center, and is the primary teaching hospital for UCI Health School of Medicine. UCI Health serves a region of more than 3 million people in Orange County, western Riverside County and southeast Los Angeles County.

About the University of California, Irvine: Founded in 1965, UCI is a top-ranked university dedicated to research, scholarship and community service. Led by Chancellor Michael Drake since 2005, UCI is among the most dynamic campuses in the University of California system, with more than 28,000 undergraduate and graduate students, 1,100 faculty and 9,400 staff. Orange County’s second-largest employer, UCI contributes an annual economic impact of $4.3 billion. For more UCI news, visit news.uci.edu.