Researchers have found that the novel intravesical chemotherapy delivery system TAR-200 may be safe and effective for patients with advanced muscle-invasive bladder cancer who are medically unfit for standard treatment, according to a new study published by Tyson et al in The Journal of Urology. TAR-200 is a small drug-device combination product that is implanted into the bladder, where it can provide a continuous, low-dose, local delivery of gemcitabine.
Background
The goal of this type of treatment is to limit cancer growth or progression while also minimizing the toxic effects of chemotherapy.
"Our preliminary clinical trial found that [the] TAR-200 [device] was generally safe, well tolerated, and had beneficial effects on bladder cancer outcomes in a group of patients with limited treatment options," explained lead study author Mark Tyson II, MD, MPH, a urologic oncologist at the Mayo Clinic Arizona.
By the time of diagnosis, about 25% of bladder cancers have spread into the muscle layer of the bladder wall. For these muscle-invasive bladder cancers, chemotherapy followed by surgery is the standard treatment. However, some patients are considered medically unfit for or decline to pursue this treatment, which carries substantial rates of complications and adverse effects. Additionally, previous studies have found that 25% to 57% of patients across the world who have muscle-invasive bladder cancer may not receive any curative-intent therapy.
"This suggests a critical need for alternative therapies that are tolerable and effective in an elderly population," the researchers stressed.
Study Methods and Results
In the new phase I study, the researchers examined the safety and efficacy of TAR-200 in 35 patients with a median age of 84 years who had muscle-invasive bladder cancer. The patients were deemed medically ineligible for standard radical cystectomy and chemotherapy or opted not to receive standard treatment. All of the patients underwent minimally invasive transurethral resection of bladder tumor to remove any visible tumors.
The patients then underwent a simple procedure to implant the TAR-200 device, which released gemcitabine over the course of 21 days. At that time, another procedure was performed to remove and replace the device, for a total of four treatments over 84 days.
After follow-up, the researchers determined that the TAR-200 device was safe and well tolerated. About 25% of the patients involved in the study had problems related to device placement or treatment procedures, and about 40% of them experienced treatment-related adverse events—most commonly, problems with urination. The researchers found these side effects to be relatively minor and expected in a cohort of elderly patients with muscle-invasive bladder cancer. Two of the patients were considered intolerant to treatment with the TAR-200 device, requiring device removal.
Overall, 31.4% (n = 11/35) of the patients had a complete response to the TAR-200 device, with no evidence of bladder cancer at follow-up. Further, 8.6% (3/35) of the patients had a partial response, for an overall response rate of 40%. The median overall survival was about 27 months. Among 14 patients with lasting responses to treatment with the TAR-200 device, the 12-month progression-free survival rate was 70.5%.
Conclusions
"Overall, the observed clinical response to [the] TAR-200 [device] was robust and durable in a cohort with very limited curative-intent treatment options," the researchers reported. However, they noted that there were several limitations to the study—including the low amount of participants, the lack of a comparison group, and incomplete assessment of response rates.
"Despite these limitations, the safety, patient tolerance, and promising preliminary effects of [the] TAR-200 [device] warrant further study as an alternative treatment for [patients with muscle-invasive bladder cancer],” concluded Dr. Tyson.
Disclosure: For full disclosures of the study authors, visit auajournals.org.
