title: A phase II trial of temsirolimus in second-line metastatic urothelial cancer.
abstract: This phase II trial assessed temsirolimus, an inhibitor of mammalian target of rapamycin (mTOR), as second-line therapy in patients with metastatic transitional carcinoma of the urothelium (TCCU) after failure of platinum containing therapy. From June/2009 to June/2011, we enrolled 15 patients in this trial. Primary endpoint was overall survival, as secondary endpoints we defined time to disease progression, safety and QoL along treatment. Patients with progressive TCCU after prior platinum-based chemotherapy received weekly 25 mg of temsirolimus for 8 weeks. Evaluation for response was accomplished every 8 weeks according to the RECIST criteria, QoL assessment was done every 4 weeks using the QLQ-C30 questionnaire, adverse events (AEs) were recorded and graded using NCI-CTC criteria. Fifteen patients were enrolled in this study, of whom 14 (93%) were available for activity, safety and QoL assessment. We treated 10 (71%) male and 4 female (29%) patients. Median age was 64,7 years (45-76). Patients received on average 13 (3-15) infusions of temsirolimus. As per protocol, no sufficient benefit on overall survival was observed, we early stopped the study after 14 patients. Median time to progression was 2.5 months (77 days), median overall survival was 3.5 months (107 days). Four patients with stable disease were observed. QoL assessment along treatment revealed a reduction of EORTC-QLQ-C30, Global Health Status subscale, from initial 7.86 to 5.00. Temsirolimus was well tolerated. As Grade 3-4 adverse events, we observed fatigue (n=2), leukopenia (n=2) and thrombopenia (n=2). All other adverse events were graded 1-2 in nature. Temsirolimus seems to have poor activity in patients with progressive metastasized TCCU after failure of platinum containing first-line therapy.
authors.affiliation: Department of Urology, Lukas Hospital, Preussenstrasse 84, 41464, Neuss, Germany. holger.gerullis@gmx.net
authors.forename: H
authors.initials: H
authors.lastname: Gerullis
authors.forename: C
authors.initials: C
authors.lastname: Eimer
authors.forename: T H
authors.initials: TH
authors.lastname: Ecke
authors.forename: E
authors.initials: E
authors.lastname: Georgas
authors.forename: C
authors.initials: C
authors.lastname: Freitas
authors.forename: S
authors.initials: S
authors.lastname: Kastenholz
authors.forename: C
authors.initials: C
authors.lastname: Arndt
authors.forename: C
authors.initials: C
authors.lastname: Heusch
authors.forename: T
authors.initials: T
authors.lastname: Otto
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011788:Quality of Life; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C401859:temsirolimus; D020123:Sirolimus