"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.
[Authors' affiliations: 16 institutions worldwide]
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
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 58 times in current journal articles
indexed by Clarivate Analytics during September-October 2008. Repeating its
performance from the previous count for July-August, the report registers
as the second-most-cited medicine paper, aside from reviews, published in
the last two years. Prior to the most recent bimonthly count, citations to
the paper have accrued as follows:
July-August 2008: 58 citations
May-June 2008: 41
March-April 2008: 59
January-February 2008: 42
November-December 2007: 34
September-October 2007: 38
July-August 2007: 23
May-June 2007: 10
March-April 2007: 3
January-February 2007: 1
Total citations to date: 384
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