Temsirolimus safety profile and management of toxic effects in patients with advanced renal cell carcinoma and poor prognostic features

• Published in: Annals of oncology Vol. 19; no. 8; pp. 1387 - 1392
• Main Authors: Bellmunt, J., Szczylik, C., Feingold, J., Strahs, A., Berkenblit, A.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.08.2008; Oxford University Press; Oxford Publishing Limited (England)
• Subjects: Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carcinoma, Renal Cell - drug therapy; Female; Humans; interferon; Interferon-alpha - adverse effects; Interferon-alpha - therapeutic use; Kidney Neoplasms - drug therapy; Kidneys; Male; mammalian target of rapamycin (mTOR); Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Pharmacology. Drug treatments; renal cell carcinoma; safety; Sirolimus - adverse effects; Sirolimus - analogs & derivatives; Sirolimus - therapeutic use; temsirolimus; Tumors of the urinary system; mammalian target of rapamycin (mTOR); renal cell carcinoma; temsirolimus; interferon; safety; Kidney disease; Antineoplastic agent; Human; Protein kinase mTOR; Urinary system disease; Carcinoma; Prognosis; Toxicity; Cytokine; Temsirolimus; Malignant tumor; Clinical management; Kidney cancer; Mammalian target of rapamycin; Grawitz tumor; Advanced stage; Interferon; Cancer
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdn066

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 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. 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. 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.