"Sorafenib in advanced clear-cell renal-cell carcinoma,"
by Bernard Escudier and 18 others, for the TARGET
Study Group, New England Journal of Medicine, 356(2): 125-34, 11
January 2007.
Abstract: "BACKGROUND We conducted a
phase 3, randomized, double-blind, placebo-controlled trial of sorafenib, a
multikinase inhibitor of tumor-cell proliferation and angiogenesis, in
patients with advanced clear-cell renal-cell carcinoma.
METHODS From November 2003 to March 2005, we randomly
assigned 903 patients with renal-cell carcinoma that was resistant to
standard therapy to receive either continuous treatment with oral sorafenib
(at a dose of 400 mg twice daily) or placebo; 451 patients received
sorafenib and 452 received placebo. The primary end point was overall
survival. A single planned analysis of progression-free survival in January
2005 showed a statistically significant benefit of sorafenib over placebo.
Consequently, crossover was permitted from placebo to sorafenib, beginning
in May 2005. RESULTS At the
January 2005 cutoff, the median progression-free survival was 5.5 months in
the sorafenib group and 2.8 months in the placebo group (hazard ratio for
disease progression in the sorafenib group, 0.44; 95% confidence interval
[CI], 0.35 to 0.55; P<0.01). The first interim analysis of overall
survival in May 2005 showed that sorafenib reduced the risk of death, as
compared with placebo (hazard ratio, 0.72; 95% CI, 0.54 to 0.94; P=0.02),
although this benefit was not statistically significant according to the
O'Brien-Fleming threshold. Partial responses were reported as the best
response in 10% of
patients receiving sorafenib and in 2% of those receiving placebo
(P<0.001). Diarrhea, rash, fatigue, and hand-foot skin reactions were
the most common adverse events associated with sorafenib. Hypertension and
cardiac ischemia were rare serious adverse events that were more common in
patients receiving sorafenib than in those receiving placebo.
CONCLUSIONS As compared with placebo, treatment with
sorafenib prolongs progression-free survival in patients with advanced
clear-cell renal-cell carcinoma in whom previous therapy has failed;
however, treatment is associated with increased toxic effects."
This 2007 report from the New England Journal of Medicine was
cited 59 times in current journal articles
indexed by Clarivate during March-April 2008. Only two other medicine
papers published in the last two years, excluding reviews, garnered higher
citation totals during that two-month period. Prior to the most
recent bimonthly count, citations to the paper have accrued as follows:
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