A phase II trial of sorafenib in first-line metastatic urothelial cancer: a study of the PMH Phase II Consortium

• Published in: Investigational new drugs 2011-10, Vol.29 (5), p.1045-1049
• Main Authors: Sridhar, Srikala S., Winquist, Eric, Eisen, Andrea, Hotte, Sebastien J., McWhirter, Elaine, Tannock, Ian F., Mukherjee, Som D., Wang, Lisa, Blattler, Chantale, Wright, John J., Moore, Malcolm J.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Angiogenesis; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Benzenesulfonates - adverse effects; Benzenesulfonates - therapeutic use; Cancer therapies; Cell growth; Chemotherapy; Clinical trials; Consent; Consortia; Drug withdrawal; Drugs; Female; Humans; Inhibitor drugs; Kinases; Male; Medicine; Medicine & Public Health; Metastasis; Middle Aged; Mutation; Neoplasm Metastasis; Niacinamide - analogs & derivatives; Oncology; Patients; Pharmacology; Pharmacology/Toxicology; Phase II Studies; Phenylurea Compounds; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Pyridines - adverse effects; Pyridines - therapeutic use; Radiation; Response rates; Studies; Toxicity; Treatment Outcome; Urologic Neoplasms - drug therapy; Urologic Neoplasms - pathology; Urothelium - pathology; Vascular endothelial growth factor
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-010-9408-4

Summary Background Sorafenib is an oral multikinase inhibitor that blocks cell proliferation via the ERK pathway and angiogenesis via the VEGF pathway. This phase II trial was conducted to determine the efficacy and tolerability of sorafenib for the treatment of patients with metastatic urothelial cancer (UC) who had not had prior chemotherapy for advanced disease. Patients and Methods Seventeen chemo-naïve UC patients with adequate performance status and organ function were treated with sorafenib 400 mg twice daily on a continuous basis until progression or unacceptable toxicity. The primary endpoint was objective tumor response rate as measured by RECIST criteria. Secondary endpoints included rate of prolonged stable disease (>3 months), time to progression, median and 1 yr survival and safety and tolerability. Results There were no objective responses. Only one patient had stable disease by RECIST criteria and remained on treatment more than 3 months. Three patients had stable disease by RECIST criteria but were on treatment less than 3 months due to progressive disease (PD) or adverse events (AE). Eight patients had PD by RECIST criteria as their best overall response. Two patients had symptomatic PD prior to cycle 2 evaluation, and three patients were inevaluable (1 death, 1 AE, 1 withdrew consent).The time to progression was 1.9 months (range 0.7–8.7 months) and median survival was 5.9 months. The most common grade 3+ toxicities were abdominal pain, back pain, hand-foot reaction and bladder infection. Conclusions Sorafenib does not show sufficient activity as a single agent in first-line metastatic urothelial cancer to warrant further investigation.