UCLA cancer researchers are seeking hundreds of former smokers who have had bladder cancer to test a green tea extract and a molecularly targeted therapy to determine if the agents will prevent recurrence of the disease.

The study, by scientists and physicians at UCLA's Jonsson Comprehensive Cancer Center, the School of Public Health and the departments of Urology, Medicine, Pathology, is part of a first-of-its-kind, comprehensive program to prevent the recurrence and progression of smoking-related bladder cancer, which accounts for about half of all bladder cancers.

In additional to the clinical trial, conducted at UCLA and two other sites nationwide, researchers also will develop biomarker tests to help predict who will get bladder cancer, discover the molecular profile of the disease to identify those most at risk and create a tumor bank to aid in scientific research.

Funded by a $7 million grant from the National Cancer Institute (NCI) with supplemental funds from the NCI Office of Complementary and Alternative Medicine, the five-year program is headed by Dr. Arie Belldegrun, a cancer researcher, chief of the division of urologic oncology and a professor of urology. It is the largest prevention study in the United States sponsored by the NCI to focus on bladder cancer in former smokers, Belldegrun said, and the first study approved by the U.S. Food and Drug Administration to use a new class of experimental drug in the prevention of any type of cancer.

The clinical trial will test the experimental drugs Polyphenon E, a green tea extract (Tokyo Food Techno), and the drug Tarceva (Genentech/OSI Pharmaceuticals), which has been shown to reduce the growth of advanced cancers in patients with lung and other epithelial cell tumors. Led Belldegrun, Dr. Robert Figlin, a professor of hematology/oncology and urology, and Dr. Allan Pantuck, an assistant professor of urology, the study will divide participants into three treatment arms. One group will receive the green tea extract, which has been shown in UCLA and other laboratories to reduce the growth of bladder cancer tumors both in animal models and in humans. The second group will receive Tarceva, while the third group will receive a placebo.

"We will study innovative approaches to reduce the risk of bladder cancer," Belldegrun said. "And while we'll study how to prevent cancer recurrence and progression in former smokers who have already had bladder cancer, our goal is to develop effective prevention strategies for people who may be at risk but who do not yet have bladder cancer."

Bladder cancer is the fifth most common cancer in the United States, with more than 56,000 new cases diagnosed each year. As many as half of all bladder cancers are believed to be related to cigarette smoking. Without a reliable, non-invasive way to diagnose the disease, bladder cancer can be difficult to detect in the early, most treatable stages. When not found early, these tumors typically are very aggressive, with more than half of advanced bladder cancer patients experiencing recurrences.

No one yet knows all of the causes of bladder cancer. Risk factors besides tobacco smoking include age, being a man - men are two to three times more likely to get bladder cancer than women - family history and race - Caucasians are two to three times more likely to get bladder cancer than African Americans, Latinos or Asians. Smoking-related bladder cancer has a 20-year latency period, UCLA researchers said, meaning that it takes about 20 years for the cancer to develop in smokers and former smokers.

Not all smokers and former smokers develop bladder cancer and UCLA researchers want to find out why.

"We're looking for specific biologic signals that tell us why some people get this disease and others don't," Figlin said. "We want to decrease bladder cancer occurrence and develop molecular profiles that tell us who is most at risk."

Symptoms of bladder cancer include blood in the urine, pain during urination and frequent urination or the need to urinate without results.