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Week of October 3, 2010

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"Sorafenib in advanced hepatocelluar carcinoma," by Josep M. Llovet and 22 others, New England Journal of Medicine, 359(4): 378-90, 24 July 2008..


[Authors' affiliations: 20 institutions worldwide]

Abstract: "Background No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma.

Methods In this multicenter, phase 3, double-blind, placebo-controlled trial, we randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or placebo. Primary outcomes were overall survival and the time to symptomatic progression. Secondary outcomes included the time to radiologic progression and safety.

Results At the second planned interim analysis, 321 deaths had occurred, and the study was stopped. Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (hazard ratio in the sorafenib group, 0.69; 95% confidence interval, 0.55 to 0.87; P<0.001). There was no significant difference between the two groups in the median time to symptomatic progression (4.1 months vs. 4.9 months, respectively, P=0.77). The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group (P<0.001). Seven patients in the sorafenib group (2%) and two patients in the placebo group (1%) had a partial response; no patients had a complete response. Diarrhea, weight loss, hand-foot skin reaction, and hypophosphatemia were more frequent in the sorafenib group.

Conclusions In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo."

This 2008 report from the New England Journal of Medicine was cited 62 times in current journal articles indexed by Thomson Reuters during May-June 2010. Based on this latest two-month tally, the report is currently the second-most-cited medicine paper published in the last two years, aside from reviews. Prior to the most recent bimonthly count, citations to the paper have accrued as follows:

March-April 2010: 53 citations
January-February 2010: 51
November-December 2009: 48
September-October 2009: 44
July-August 2009: 51
May-June 2009: 45
March-April 2009: 33
January-February 2009: 37
November-December 2008: 16
September-October 2008: 4
July-August 2008: 2

Total citations to date: 446


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.

 
 

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