Originally published as JCO Early Release 10.1200/JCO.2009.22.0541 on August 3 2009

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Phase II, Multicenter, Uncontrolled Trial of Single-Agent Sorafenib in Patients With Relapsed or Refractory, Advanced Non–Small-Cell Lung Cancer

From the University of Texas M. D. Anderson Cancer Center, Houston, TX; Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf, Germany; and Bayer HealthCare Pharmaceuticals, Montville, NJ.

Corresponding author: George R. Blumenschein Jr, MD, The M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 432, Houston, TX 77030-4009; email: gblumens{at}mdanderson.org.

Purpose Sorafenib is an oral multikinase inhibitor that targets the Ras/Raf/MEK/ERK mitogenic signaling pathway and the angiogenic receptor tyrosine kinases, vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor β. We evaluated the antitumor response and tolerability of sorafenib in patients with relapsed or refractory, advanced non–small-cell lung cancer (NSCLC), most of whom had received prior platinum-based chemotherapy.

Patients and Methods This was a phase II, single-arm, multicenter study. Patients with relapsed or refractory advanced NSCLC received sorafenib 400 mg orally twice daily until tumor progression or an unacceptable drug-related toxicity occurred. The primary objective was to measure response rate.

Results Of 54 patients enrolled, 52 received sorafenib. The predominant histologies were adenocarcinoma (54%) and squamous cell carcinoma (31%). No complete or partial responses were observed. Stable disease (SD) was achieved in 30 (59%) of the 51 patients who were evaluable for efficacy. Four patients with SD developed tumor cavitation. Median progression-free survival (PFS) was 2.7 months, and median overall survival was 6.7 months. Patients with SD had a median PFS of 5.5 months. Major grades 3 to 4, treatment-related toxicities included hand-foot skin reaction (10%), hypertension (4%), fatigue (2%), and diarrhea (2%). Nine patients died within a 30-day period after discontinuing sorafenib, and one patient experienced pulmonary hemorrhage that was considered drug related.

Conclusion Continuous treatment with sorafenib 400 mg twice daily was associated with disease stabilization in patients with advanced NSCLC. The broad activity of sorafenib and its acceptable toxicity profile suggest that additional investigation of sorafenib as therapy for patients with NSCLC is warranted.

This research was supported by Bayer Healthcare Pharmaceuticals, Montville, NJ, and by Onyx Pharmaceuticals, Richmond, CA.

Presented at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA, and at the American Association for Cancer Research/European Organisation for Research and Treatment of Cancer/National Cancer Institute Conference on Molecular Targets and Cancer Therapeutics, November 12-14, 2005, Philadelphia, PA.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

Clinical trial information can be found for the following: NCT00101413 [ClinicalTrials.gov] .

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