Pan awarded grant to test 'smart' chemotherapy drug for bladder cancer
Clinical trial may improve survival rates and transform the standard of care
UC Davis Comprehensive Cancer Center oncologist Chong-Xian Pan has received a $650,000 grant from the VA Northern California Health Care System to conduct the first clinical trial of a novel chemotherapy-delivery drug he developed for bladder cancer patients.
Bladder cancer is one of the 10 most common cancers in the United Sates, however, there has been very little improvement in treatment outcomes during the past three decades said Pan, a genitourologist, the study’s principal investigator, and leader of the Urothelial Carcinoma Initiative at the Comprehensive Cancer Center.
The researchers hope the trial will result in a more effective therapy and improved treatment outcomes and possibly a cure for bladder cancer.
Standard treatment for non-muscle invasive bladder cancer, which accounts for 80 percent of cases, currently is “intravesical therapy,” which involves a transurethral resection of bladder tumor, a proceure in which a scope is inserted into the patient’s bladder through the urethra and the cancerous cells are removed with a cutting tool. Most patients then are given a vaccine commonly used to prevent tuberculosis, which stimulates immune cells that can kill bladder cancer cells.
“And that is not good enough,” said Pan, associate professor in the UC Davis Division of Hematology and Oncology.
In 60 percent of cases the cancer returns within two years, Pan said. When it does, oncologists reach for valrubicin, the only Food and Drug Administration-approved drug for recurrent bladder cancer. But valrubicin only works 20 percent of the time.
So Pan and Kit Lam, study co-investigator and chair of the UC Davis Department of Biochemistry and Molecular Medicine, developed a micelle that targets bladder cancer cells and loads them with Paclitaxel, a chemotherapy agent commonly used to treat bladder cancer. The micelle is coated with a PLZ4 ligand, developed by Lam and Pan. Together the ligand-coated micelle enhances Paclitaxel’s effectiveness while decreasing its toxicity.
“It’s like a guided missile,” Pan said.
“Without creating much toxicity, the cancer-targeting micelle has proven effective in killing human bladder cancer cells when injected into a mouse model,” he said. “The goal is to now determine the drug’s safety and effectiveness in humans.”
If found to be effective in humans, it could decrease the recurrence and prevent progression of bladder cancer, reducing the need for regular cystoscopies, Pan said.
Bladder cancer is the most expensive type of cancer to treat because the recurrence rate is so high and patients must have regular cystoscopies, which are invasive and costly.
“We hope that, with this new drug, we can decrease recurrence, discomfort for patients, and cost,” Pan said.
Starting next year, Pan and his colleagues will recruit patients for the Phase I clinical trial, testing the new targeted therapy in veterans with non-muscle-invasive bladder cancer who have had intravesical therapy.
Each patient will receive the drug once a week for six weeks. Phase I testing will take place over the next four years to determine the recommended dose for phase II, in which the same drug formulation will be tested on a larger population.
“If this works, the drug formulation could become the new standard of care and is a potential successful treatment for bladder cancer,” Pan said.
UC Davis Comprehensive Cancer Center is the only National Cancer Institute-designated center serving the Central Valley and inland Northern California, a region of more than 6 million people. Its specialists provide compassionate, comprehensive care for more than 10,000 adults and children every year, and access to more than 150 clinical trials at any given time. Its innovative research program engages more than 280 scientists at UC Davis, Lawrence Livermore National Laboratory and Jackson Laboratory (JAX West), whose scientific partnerships advance discovery of new tools to diagnose and treat cancer. Through the Cancer Care Network, UC Davis collaborates with a number of hospitals and clinical centers throughout the Central Valley and Northern California regions to offer the latest cancer care. Its community-based outreach and education programs address disparities in cancer outcomes across diverse populations. For more information, visit cancer.ucdavis.edu.