Annals of Oncology Advance Access originally published online on April 2, 2008
Annals of Oncology 2008 19(8):1387-1392; doi:10.1093/annonc/mdn066
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oncology practice |
Temsirolimus safety profile and management of toxic effects in patients with advanced renal cell carcinoma and poor prognostic features
1 Oncology Department, University Hospital del Mar, Barcelona, Spain
2 Klinika Onkologii Wojskowy Instytut Medyczny, Warszawa, Poland
3 Wyeth Research, Cambridge, MA, 02140 USA
* Correspondence to: Dr J. Bellmunt, Solid Tumor Oncology (Genitourinary & Gastrointestinal), Medical Oncology Service, Hospital del Mar, Paseo Maritimo 25–29, Barcelona 08003, Spain. Tel: +34-93-2483137; Fax: +34-93-2483366; E-mail: jbellmunt{at}imas.imim.es
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.
Key words: interferon, mammalian target of rapamycin (mTOR), renal cell carcinoma, safety, temsirolimus
Received for publication October 11, 2007. Revision received January 7, 2008. Accepted for publication February 20, 2008.
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