J Bellmunt1, C Szczylik2, J Feingold3, A Strahs3, A Berkenblit3. 1. Oncology Department, University Hospital del Mar, Barcelona, Spain. Electronic address: jbellmunt@imas.imim.es. 2. Klinika Onkologii Wojskowy Instytut Medyczny, Warszawa, Poland. 3. Wyeth Research, Cambridge, MA, 02140 USA.
Abstract
BACKGROUND: Temsirolimus, a novel inhibitor of mammalian target of rapamycin, has demonstrated prolonged overall survival and progression-free survival compared with interferon alfa (IFN) in patients with advanced renal cell carcinoma (RCC) and poor prognostic features. Adverse events (AEs) of any causality were previously reported, but AEs that were deemed temsirolimus related are of particular relevance for poor-risk patients and for defining mammalian target of rapamycin inhibitor-specific side-effects. PATIENTS AND METHODS: Patients with advanced RCC, no prior systemic therapy, and three or more of six poor-risk factors were randomly assigned to one of three groups: (i) IFN s.c. up to 18 MU thrice weekly, (ii) temsirolimus i.v. 25 mg weekly, or (iii) temsirolimus i.v. 15 mg weekly plus interferon s.c. 6 MU thrice weekly. RESULTS: Among 208 patients, the most common temsirolimus-related grades 3-4 AEs were anemia (13%), hyperglycemia (9%), and asthenia (8%). Grades 3-4 hypercholesterolemia (1%), hypertriglyceridemia (3%), and hypophosphatemia (4%) were also seen. Although pneumonitis occurred infrequently, vigilance for its development is needed. Guidelines for management of toxic effects are presented on the basis of available clinical experience. CONCLUSIONS: Temsirolimus-related grades 3-4 AEs were primarily metabolic in nature and easily controlled medically. In general, these did not negatively impact patient quality of life.
RCT Entities:
BACKGROUND:Temsirolimus, a novel inhibitor of mammalian target of rapamycin, has demonstrated prolonged overall survival and progression-free survival compared with interferon alfa (IFN) in patients with advanced renal cell carcinoma (RCC) and poor prognostic features. Adverse events (AEs) of any causality were previously reported, but AEs that were deemed temsirolimus related are of particular relevance for poor-risk patients and for defining mammalian target of rapamycin inhibitor-specific side-effects. PATIENTS AND METHODS: Patients with advanced RCC, no prior systemic therapy, and three or more of six poor-risk factors were randomly assigned to one of three groups: (i) IFN s.c. up to 18 MU thrice weekly, (ii) temsirolimus i.v. 25 mg weekly, or (iii) temsirolimus i.v. 15 mg weekly plus interferon s.c. 6 MU thrice weekly. RESULTS: Among 208 patients, the most common temsirolimus-related grades 3-4 AEs were anemia (13%), hyperglycemia (9%), and asthenia (8%). Grades 3-4 hypercholesterolemia (1%), hypertriglyceridemia (3%), and hypophosphatemia (4%) were also seen. Although pneumonitis occurred infrequently, vigilance for its development is needed. Guidelines for management of toxic effects are presented on the basis of available clinical experience. CONCLUSIONS:Temsirolimus-related grades 3-4 AEs were primarily metabolic in nature and easily controlled medically. In general, these did not negatively impact patient quality of life.
Authors: Scott Okuno; Howard Bailey; Michelle R Mahoney; Douglas Adkins; William Maples; Tom Fitch; David Ettinger; Charles Erlichman; Jann N Sarkaria Journal: Cancer Date: 2011-02-01 Impact factor: 6.860
Authors: Bradley J Atkinson; Diana H Cauley; Chaan Ng; Randall E Millikan; Lianchun Xiao; Paul Corn; Eric Jonasch; Nizar M Tannir Journal: BJU Int Date: 2013-12-02 Impact factor: 5.588