Open AccessTemsirolimus in the treatment of advanced renal cell carcinoma
Author(s) -
Bernard Escudier
Publication year - 2011
Publication title -
oncology reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.637
H-Index - 21
eISSN - 1970-5565
pISSN - 1970-5557
DOI - 10.4081/oncol.2007.142
Subject(s) - temsirolimus , medicine , renal cell carcinoma , refractory (planetary science) , discovery and development of mtor inhibitors , oncology , gastroenterology , urology , pi3k/akt/mtor pathway , apoptosis , biochemistry , chemistry , physics , astrobiology
Temsirolimus is a novel inhibitor of mammalian target of rapamycin (mTOR), which is a central regulator of the response of tumour cells to growth and survival signals. When heavily pretreated patients with advanced solid tumours received intravenous (IV) temsirolimus over a broad dose range, antitumour activity was observed in various tumour types, including advanced renal cell carcinoma (RCC). A study of singleagent temsirolimus in patients with cytokine-refractory metastatic RCC subsequently demonstrated antitumour activity and encouraging progression- free survival and overall survival. Temsirolimus was generally well tolerated over the 3 dose levels tested (25 mg, 75 mg or 250 mg weekly as a 30-minute IV infusion). The most frequent grade 3 or 4 treatment-related adverse events reported (n=110) were hyperglycemia (17%), hypophosphatemia (13%), anemia (9%), and hypertriglyceridemia (6%). Results from a randomized phase III study that enrolled previously untreated patients with advanced RCC and poor-prognostic features have recently demonstrated a significant increase in overall survival (p=0.0089) for patients who received temsirolimus 25 mg IV, 30-minute infusion once weekly compared with those who received interferon-alpha up to 18 million units subcutaneously thrice weekly. On the basis of improved survival, temsirolimus can be considered a first-line treatment for patients with advanced RCC.