Temsirolimus improves survival in metastatic renal cancer
Temsirolimus — developed by Wyeth — improves the overall survival of patients with advanced renal cancer when compared with interferon alfa, a phase III study shows (New England Journal of Medicine 2007;356:2271).
Researchers studied a total of 626 patients with metastatic renal cell
carcinoma and a poor prognosis in the multi-centre trial. Patients received
intravenous temsirolimus 25mg once weekly, interferon alfa 3 million
units (increasing to 18 million units) subcutaneously three times a week,
or a combination of temsirolimus 15mg once a week plus 6 million units
of interferon alfa three times a week.
The researchers found that patients in the temsirolimus-only group had
longer overall survival (hazard ratio for death 0.73, 95 per cent confidence
interval 0.58–0.92; P=0.008) than patients receiving only interferon.
The combination treatment was not superior to interferon in terms of
overall survival.
Fewer patients in the temsirolimus group had serious side effects than
those in the interferon group. The combination treatment group had the
greatest number of patients with more serious side effects and subsequent
treatment delays, and the mean dose of temsirolimus was also lower, which,
the authors say, “could explain the failure of the combination
therapy to improve overall survival more than interferon alone”.
They add that it is also possible that the high rate of serious adverse
events reduced overall survival in the combination group.
Temsirolimus (formerly CCI-779) was designed as an ester analogue of
sirolimus
(rapamycin) to improve the unfavourable pharmaceutical properties of
sirolimus — such as poor aqueous solubility and instability — that
limited its usefulness as an anti-cancer drug. Temsirolimus is primarily
metabolised to sirolimus and both drugs specifically inhibit the protein
kinase mTOR (mammalian target of rapamycin).
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