"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 (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 Thomson Reuters 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:

January-February 2008: 42 citations
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: 210

SOURCE: Hot Papers Database (Included with a subscription to the print newsletter Science Watch^®, available from the Research Services Group of Thomson Reuters. Packaged on a CD that is mailed with each Science Watch issue, the Hot Papers Database contains data on hundreds of highly cited papers published during the last two years. User interface permits searching by author, organization, journal, field, and more. Total citations, as well as citations accrued during successive bimonthly periods, can be assessed and graphed. An updated CD containing the most recent bimonthly data is mailed with every new issue of Science Watch, six times a year. The CD also includes an electronic version of the Science Watch issue in HTML format, for personal desktop access.