MILAN – Pazopanib has antitumor activity in heavily pretreated patients with relapsed or refractory urothelial carcinoma, data from an ongoing phase II study have shown.
The early findings of the trial, which began in February 2010 and is expected to run for 2 years, suggest that the antiangiogenic agent produces a partial response or stable disease in the majority of patients.
The median time on treatment to date is 3 months, and nearly two-thirds of patients (64.7%) were progression free at 2 months, Dr. Andrea Necchi of the Fondazione IRCCS Instituo Nazionale dei Tumori in Milan reported Oct. 11.
“Bladder cancer is a common cancer worldwide ... and despite promising results achieved with first-line chemotherapy there has been no substantial improvement over the past 20 years and effective second-line chemotherapy is still lacking,” Dr. Necchi observed during a presentation at the annual congress of the European Society for Medical Oncology.
Urothelial cancer is an aggressive disease, which remains essentially incurable when it becomes metastatic, he added. Pazopanib (Votrient), a multitargeted tyrosine kinase inhibitor, is already approved in the United States and Europe for the treatment of advanced renal cell carcinoma.
The target accrual of the trial is 41 patients, and in all, 18 (17 evaluable) patients have been recruited to date. The median age of participants so far is 65 years, and 55% have tumors primarily affecting the urinary bladder, whereas the remaining 45% have tumors primarily affecting the upper urinary tract. On average, participants have received two prior chemotherapy regimens, with almost 40% also receiving radiotherapy, and 72% having undergone some type of major surgery.
According to RECIST (Response Evaluation Criteria in Solid Tumors), four (22%) patients experienced a partial response, 11 (61%) had stable disease, and two (11%) had progressive disease following treatment with pazopanib (800 mg once daily).
The drug was well tolerated overall, with grade 3/4 nausea or anorexia reported in two (11%) patients and hypertension in one (5%) patient. Grade 1/2 adverse events observed included anemia, asthenia, diarrhea, abdominal pain, and hand-foot syndrome.
“Of course, we are only at the first step of this phase II trial, and caution is needed when interpreting the results,” Dr. Necchi said in a press statement. Although more patients need to be recruited and longer follow-up is required, “this is the first time in this disease we are generating interest among investigators and, particularly, of the pharmaceutical industry.”
Dr. Necchi noted that the trial was being conducted independently of GlaxoSmithKline, the company that manufactures pazopanib. “The study shows that it is possible in Europe to promote independent research that focuses attention on challenging problematic matters, such as salvage therapy in urothelial cancer,” he observed.
Dr. Joaquim Bellmunt of the Hospital del Mar in Barcelona said in the same press statement that “these preliminary results underline the value of angiogenesis as a target in bladder cancer. They add to the results other groups have published recently using similar drugs to treat bladder cancer.”
The Fondazione IRCCS Instituo Nazionale dei Tumori in Milan sponsored the study. Dr. Necchi has participated in advisory board meetings held by GlaxoSmithKline, manufacturer of pazopanib; his coauthors declared they had no conflicts of interest.