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Pazopanib Potential Treatment for Refractory Urothelial Cancer

TOP - Special Issue May 2012, Vol 5, No 3 published on May 24, 2012

Pazopanib, an angiogenesis inhibitor, achieved meaningful responses in about three-quarters of patients with refractory urothelial cancer in preliminary clinical trial results presented at a press briefing during the 2012 Annual Meeting of the American Association for Cancer Research (AACR) in Chicago, Illinois.

According to lead author of the study, Andrea Necchi, MD, Instituto Nazionale dei Tumori, Milan, Italy, this is the first targeted therapy to demonstrate meaningful clinical activity in patients with refractory urothelial cancer. He called the 76% rate of disease stabilization “remarkable,” noting that data on other efficacy outcomes are needed in the future.

The study also provided some new information on interleukin-8 (IL-8) levels as a potential biomarker for response. Elevated levels of IL-8, as well as rising IL-8 levels during the first 4 weeks of pazopanib treatment, were associated with tumor progression and shorter overall survival. These data need to be confirmed in further trials.

“Our data indicate that pazopanib seems to be a legitimate drug in this disease. Most interestingly, our biomarker analysis clearly pointed out the role of rising levels of circulating interleukin-8 as an early and potentially practice-changing indicator of tumor resistance and poor survival,” he said, as reported in a news release from AACR.

Second-line therapies thus far have been disappointing in advanced urothelial cancer, which has a poor prognosis. Median overall survival is about 4 to 5 months. Five-year overall survival of metastatic urothelial cancer is about 10% to 15%. Although targeted therapies are theoretically attractive in bladder cancers, thus far no beneficial strategies have been identified until this trial.

The phase 2, open-label, proof-of-concept study enrolled 41 patients with advanced or metastatic urothelial cancer. Fifty percent progressed on second-line therapy. Patients received daily pazopanib 800 mg once a day until development of disease progression or unacceptable toxicity, or withdrawal.

According to RECIST criteria (for tumor shrinkage), objective responses were seen in 7 patients and stable disease in 24 patients (total disease stabilization, 31 out of 41 patients: 76%). Median progression-free survival (PFS) was 2.6 months and median overall survival was 4.7 months. At 2 months, 61% of patients were free of progression, and durable PFS was seen in 10% of patients at a median followup of 19 months.

Last modified: July 22, 2021