title: Clinical activity of sorafenib in a previously treated advanced urothelial cancer patient.
abstract: A male patient, with advanced urothelial carcinoma, who had previously received cisplatin, was treated with sorafenib off-licence for 10.7 months. Evaluation of tumour response with computed tomography scans indicated a reduction in tumour size and necrosis of the metastases within 2 months. Progression-free survival was 10.5 months. Side effects were manageable and not beyond the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 grade 2. Molecular profiling of two of the proposed targets of sorafenib, platelet-derived growth factor receptor β and vascular endothelial growth factor receptor 2, of the patient's tumour lesion showed high and intermediate expression levels in the tumour as compared with the surrounding non-neoplastic tissue. In contrast to previous reports, we report a clinically meaningful effect of sorafenib in a patient with advanced urothelial carcinoma. Hence, it appears that a fraction of patients with this disease are sensitive to this compound. To identify subpopulations of responders, we propose that clinical trials evaluating sorafenib and other targeted drugs should be biomarker-driven and designed with endpoints that consider the mode of action of the specific compound.
authors.affiliation: Department of Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden. carl-henrik.shah@karolinska.se
authors.forename: Carl-Henrik
authors.initials: CH
authors.lastname: Shah
authors.forename: Kristina
authors.initials: K
authors.lastname: Viktorsson
authors.forename: Amir
authors.initials: A
authors.lastname: Sherif
authors.forename: Lena
authors.initials: L
authors.lastname: Kanter
authors.forename: Per
authors.initials: P
authors.lastname: Grybäck
authors.forename: Rolf
authors.initials: R
authors.lastname: Lewensohn
authors.forename: Per
authors.initials: P
authors.lastname: Sandström
authors.forename: Sten
authors.initials: S
authors.lastname: Nilsson
authors.forename: Anders
authors.initials: A
authors.lastname: Ullén
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D000077157:Sorafenib; D019459:Urothelium / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib