UC Davis develops new drug for bladder cancer patients

A new drug developed at UC Davis Health could provide a safer and more effective option for bladder cancer patients, reducing chemotherapy toxicity and potentially limiting the need for bladder removal surgery.

The therapy, known as PLZ4-coated paclitaxel-loaded micelles (PPM), is now being tested in a first-in-human clinical trial and has shown encouraging early results for patients with non-muscle invasive bladder cancer, according to a UC Davis Health news release.

The drug was developed by Kit S. Lam, M.D., Ph.D., a distinguished professor in the Division of Hematology and Oncology at UC Davis School of Medicine, and Chong-xian Pan, M.D., Ph.D., a former professor of medicine and urology at UC Davis Health.

The treatment involves lipid-polymer hybrid molecules that self-assemble into nanoparticles called micelles. These microscopic spheres encapsulate the chemotherapy drug paclitaxel. By packaging the drug inside the micelles, the researchers created a delivery system designed to penetrate bladder tumors more efficiently while reducing exposure to healthy tissues.

One of the first patients to receive PPM is a 74-year-old man who had been facing limited treatment options after repeated tumor recurrences. Six weeks after beginning therapy, scans revealed no evidence of bladder cancer. His clinicians reported that he has experienced only mild side effects and has been able to resume many of his daily activities.

The researchers said this early response highlights the potential for PPM to offer more durable control compared with conventional intravesical chemotherapy.

The development of PPM is a collaboration between UC Davis clinician-scientists and materials engineers who set out to solve one of bladder cancer’s longstanding challenges, which is how to deliver high concentrations of chemotherapy directly into tumor cells without harming the rest of the body. Paclitaxel is a well-known and effective chemotherapy agent, but its toxicity limits its usefulness in bladder cancer. Encapsulating the drug in micelles may allow clinicians to use more effective doses with fewer systemic side effects.

Bladder cancer is one of the most common cancers in the United States, and non-muscle invasive disease accounts for the majority of new diagnoses. For this, patients normally undergo tumor resections followed by intravesical immunotherapy or chemotherapy to reduce the risk of recurrence. Still, many continue to experience repeated tumor growth, and some eventually require bladder removal.

UC Davis researchers noted that a treatment that improves tumor penetration while sparing healthy tissue therefore could significantly improve long-term outcomes and quality of life.

The new therapy also has practical advantages. Since the drug is delivered directly into the bladder through standard intravesical instillation, the approach could be integrated into routine clinical practice without major equipment changes, the researchers said.

The UC Davis Health team is currently studying how long the micelles persist within the bladder and whether they maintain consistent drug concentration over time. They will also track recurrence rates to assess whether the therapy may reduce the need for repeated surgeries.

The clinical trial will expand as researchers enroll additional patients to evaluate dosing, safety and durability of response. They anticipate that patients with high-grade non-muscle invasive bladder cancer, particularly those at risk for progression, may benefit most from the approach.

Furthermore, the drug’s development shows the importance of advancing targeted treatment methods that reduce harm while improving effectiveness, and the hope is if ongoing trials confirm initial findings, PPM could eventually become an alternative to radical cystectomy for some patients.

Funding for the project includes support from UC Davis and the U.S. Department of Veterans Affairs.