title: Temsirolimus safety profile and management of toxic effects in patients with advanced renal cell carcinoma and poor prognostic features.
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.
  
  
  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.affiliation: Oncology Department, University Hospital del Mar, Barcelona, Spain. Electronic address: jbellmunt@imas.imim.es.
authors.forename: J
authors.initials: J
authors.lastname: Bellmunt
authors.affiliation: Klinika Onkologii Wojskowy Instytut Medyczny, Warszawa, Poland.
authors.forename: C
authors.initials: C
authors.lastname: Szczylik
authors.affiliation: Wyeth Research, Cambridge, MA, 02140 USA.
authors.forename: J
authors.initials: J
authors.lastname: Feingold
authors.affiliation: Wyeth Research, Cambridge, MA, 02140 USA.
authors.forename: A
authors.initials: A
authors.lastname: Strahs
authors.affiliation: Wyeth Research, Cambridge, MA, 02140 USA.
authors.forename: A
authors.initials: A
authors.lastname: Berkenblit
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D016898:Interferon-alpha; C401859:temsirolimus; D020123:Sirolimus