31 juli 2009: Referentielijst met studies toegevoegd onderaan dit artikel.

25 juli 2008: Bron: 1: J Clin Oncol. 2006 Jun 1;24(16):2505-12. Epub 2006 Apr 24.Click here to read

Nevaxar (Sorafenib tosylate) remt progressie uitgezaaide niercelkanker significant t.o.v. placebo met hoewel soms ernstige bijwerkingen deze volgens de onderzoekers zijn te tolereren en goed te behandelen bijwerkingen. Deze week kwam een nieuwe studie beschikbaar en we hebben een studie uit 2006 en een fase III studie uit 2007 hieronder geplaatst die alle dezelfde goede resultaten laten zien van Nevaxar - Sorafenib tosylate bij uitgezaaide niercelkanker.  Lees hieronder het abstract van de placebo gerandomiseerde studies uit 2006 en 2007 en een artikel uit Health Day over een ook placebo gerandomiseerde fase II studie met Nevaxar - Sorafenib die deze week wordt gepubliceerd in The New England Journal of Medicine.

1: N Engl J Med. 2007 Jan 11;356(2):125-34.Click here to read Links

Erratum in:
N Engl J Med. 2007 Jul 12;357(2):203.
Comment in:
Eur Urol. 2007 Jul;52(1):279-80.
N Engl J Med. 2007 Jan 11;356(2):185-7.
Nat Clin Pract Oncol. 2007 Aug;4(8):456-7.

Sorafenib in advanced clear-cell renal-cell carcinoma.

Department of Medicine, Institut Gustave Roussy, Villejuif, France. escudier@igr.fr

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 , 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. (ClinicalTrials.gov number, NCT00073307 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Society.

PMID: 17215530 [PubMed - indexed for MEDLINE]


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Targeted Drug Boosts Survival Among Liver Cancer Patients
Sorafenib added three months for those with advanced disease, study finds

WEDNESDAY, July 23 (HealthDay News) -- The drug Nexavar can prolong the lives of people with liver cancer by an average of three months, new research shows.

"The results unequivocally showed that sorafenib (Nexavar) increased the survival of patients with a more than 30 percent reduction in the likelihood to die at any time point during follow-up," said study senior author Dr. Jordi Bruix, a senior consultant in the liver unit of the Hospital Clinic of Barcelona.

"These results identify sorafenib as the first agent that is effective in improving survival in patients with this devastating disease," said Bruix. His report is in the July 24 issue of the New England Journal of Medicine.

"Up to now, the patients diagnosed with advanced hepatocellular carcinoma had no effective treatment that could improve their survival. Now, we have an option that is based on oral treatment that is effective if liver function is still preserved," added study author Dr. Josep Maria Llovet, director of research in liver cancer at Mount Sinai School of Medicine in New York City, and a professor at the Barcelona Clinic Liver Cancer (BCLC) Group in Barcelona.

Lees artikel verder onder

Comment in:
J Clin Oncol. 2006 Oct 1;24(28):4669-70; author reply 4670-1.
Nat Clin Pract Urol. 2007 Feb;4(2):72-3.

Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma.

University of Chicago, Chicago, IL 60637, USA. mratain@medicine.bsd.uchicago.edu

PURPOSE: This phase II randomized discontinuation trial evaluated the effects of sorafenib (BAY 43-9006), an oral multikinase inhibitor targeting the tumor and vasculature, on tumor growth in patients with metastatic renal cell carcinoma.

PATIENTS AND METHODS: Patients initially received oral sorafenib 400 mg twice daily during the initial run-in period. After 12 weeks, patients with changes in bidimensional tumor measurements that were less than 25% from baseline were randomly assigned to sorafenib or placebo for an additional 12 weeks; patients with > or = 25% tumor shrinkage continued open-label sorafenib; patients with > or = 25% tumor growth discontinued treatment. The primary end point was the percentage of randomly assigned patients remaining progression free at 24 weeks after the initiation of sorafenib.

RESULTS: Of 202 patients treated during the run-in period, 73 patients had tumor shrinkage of > or = 25%. Sixty-five patients with stable disease at 12 weeks were randomly assigned to sorafenib (n = 32) or placebo (n = 33). At 24 weeks, 50% of the sorafenib-treated patients were progression free versus 18% of the placebo-treated patients (P = .0077). Median progression-free survival (PFS) from randomization was significantly longer with sorafenib (24 weeks) than placebo (6 weeks; P = .0087). Median overall PFS was 29 weeks for the entire renal cell carcinoma population (n = 202). Sorafenib was readministered in 28 patients whose disease progressed on placebo; these patients continued on sorafenib until further progression, for a median of 24 weeks. Common adverse events were skin rash/desquamation, hand-foot skin reaction, and fatigue; 9% of patients discontinued therapy, and no patients died from toxicity.

CONCLUSION: Sorafenib has significant disease-stabilizing activity in metastatic renal cell carcinoma and is tolerable with chronic daily therapy.

PMID: 16636341 [PubMed - indexed for MEDLINE]

Health Daynews



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