ESMO: Imaging reveals drug's promise in treating urothelial cancer
An ongoing Phase 2 trial investigating Pazopanib, a multitargeted drug with distinct anti-angiogenic activity for metastatic urothelial cancer has generated promising early results, according to a presentation at the 35th Congress of the European Society for Medical Oncology (ESMO) in Milan last week.

Urothelial cancers affect the tissue that lines the inner surfaces of the bladder and other parts of the urinary system. In cases of metastatic disease, median survival is approximately 12 to 15 months and there is a 10 to15 percent chance of prolonging it by the use of standard chemotherapy regimens, particularly in otherwise healthy patients with good prognostic factors. Those whose cancers relapse or do not respond to upfront therapy currently have few second-line treatment options; palliative care is the option in the majority of cases.

A Phase 2 trial using pazopanib in this setting has been begun by Andrea Necchi, MD, from Fondazione IRCCS Istituto Nazionale dei Tumori of Milan, and colleagues. Pazopanib is a selective inhibitor of several signaling pathways that contribute to tumor growth and the development of new cancer-related blood vessels (angiogenesis).

Thus far, the researchers have enrolled 18 patients of a total of 41 planned. Each participant had metastatic urothelial cancer that had already failed to respond to at least one prior chemotherapy regimen. Eight patients had urothelial cancer of the upper urinary tract while 10 had a bladder primary tumor. Also 16 out of 18 patients had multiple sites of metastases. Patients were administered 800 mg of the drug once daily until their disease progressed or they experienced unacceptable toxicity.

Necchi and colleagues investigated all patients with CT and 18FDG-PET at baseline and every month thereafter. Median follow-up was three months. Four patients had confirmed RECIST-defined partial response, 11 had a stable disease. Twelve patients had necrotic evolution of multiple metastases and/or a decreased standard uptake value at PET consistent with partial response. Results for the fully enrolled trial will be available in October, said Necchi.

“Considering this drug partly acts to prevent tumors recruiting the blood supplies they need to live and grow, necrotic evolution of metastases is not completely surprising," Necchi said. "But this is the first time we have seen this phenomenon in so many cases of urothelial cancer. The challenge is to translate this kind of activity into a survival advantage."

"A longer follow-up time and greater sample size are needed before we can declare the study a success. However, for the first time in this disease we are generating interest among investigators and, particularly, of pharmaceutical industry," Necchi added.

"These preliminary results underline the value of angiogenesis as a target in bladder cancer," commented Joaquim Bellmunt, MD, PhD, section chief in solid tumor oncology at Hospital del Mar in Barcelona, Spain. "They add to results other groups have published recently using similar drugs to treat bladder cancer," he added.