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.
- 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. email@example.com
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]
- Jemal A, Siegel R, Ward E, et al. Cancer statistics 2008. CA Cancer J Clin 2008; 58:71-96.
- Laber DA. Risk factors, classification and staging of renal cell cancer. Med Oncol 2006; 24:443-54.
- Cohen D, Zhou M, Cohen D, et al. Molecular genetics of familial renal cell carcinoma syndromes. Clin Lab Med 2005; 25:259-77.
- Awada A, Hendlisz A, Gil T, et al. Phase I safety and pharmacokinetics of BAY 439006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours. Br J Cancer 2005; 92:1855-61.
- Moore M, Hirte HW, Siu L, et al. Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors. Ann Oncol 2005; 16:1688-94.
- Strumberg D, Richly H, Hilger RA, et al. Phase I clinical and pharmacokinetic study of the Novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J Clin Oncol 2005; 23:965-72.
- Ratain MJ, Eisen T, Stadler WM, et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 2006; 24:2505-12.
- Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Eng J Med 2007; 356:125-34.
- Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada [see comment]. J Natl Cancer Inst 2000; 92:205-16.
- Knox JJ, Figlin RA, Stadler WM, et al. The advanced renal cell carcinoma sorafenib (ARCCS) expanded access trial in North America: safety and efficacy. J Clin Oncol 2007: 25(18 suppl) 237s (Abstract 5011).
- Common Terminology Criteria for Adverse Events v3.0 (CTCAE). Bethesda, MD: National Cancer Institute, 2003. Available at: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf. Accessed: December 31, 2008.
- Nexavar (sorafenib) [prescribing information]. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2008. Available at: http://berlex.bayerhealthcare.com/html/ products/pi/Nexavar_PI.pdf. Accessed: December 31, 2008.
- Data on File. Bayer Pharmaceuticals. NDA 15.6 (188.8.131.52.1).
Targeted Drug Boosts Survival Among Liver Cancer Patients
Sorafenib added three months for those with advanced disease, study finds
By Serena Gordon
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
- Nexavar(R) (sorafenib tosylate) geeft ook bescheiden doch goed resultaat bij nierkankerpatienten met uitzaaiingen t.o.v. placebo waar andere behandelingen faalden. Aldus kleine studie met 14 uitbehandelde nierkankerpatienten.
- Nexavar(R) (sorafenib tosylate): FDA geeft officieel toestemming voor gebruik van Nexavar(R) (sorafenib tosylate) bij vervorderde niercelkanker
- Regulier - nierkanker: actuele ontwikkelingen en belangrijke studies binnen de reguliere oncologie: een overzicht