Premium
A front‐line window of opportunity phase 2 study of sorafenib in patients with advanced nonsmall cell lung cancer
Author(s) -
Dy Grace K.,
Hillman Shauna L.,
Rowland Kendrith M.,
Molina Julian R.,
Steen Preston D.,
Wender Donald B.,
Nair Suresh,
Mandrekar Sumithra,
Schild Steven E.,
Adjei Alex A.
Publication year - 2010
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.25448
Subject(s) - medicine , sorafenib , adverse effect , clinical endpoint , population , lung cancer , stage (stratigraphy) , gastroenterology , progressive disease , surgery , mucositis , pleural effusion , oncology , radiation therapy , disease , clinical trial , hepatocellular carcinoma , paleontology , environmental health , biology
BACKGROUND: The current study was conducted to assess the efficacy and toxicity of sorafenib as front‐line therapy in patients with stage IIIB (pleural effusion) or IV nonsmall cell lung cancer (NSCLC). METHODS: Patients received sorafenib 400 mg twice daily by mouth continuously, and were evaluated every 2 weeks during the first 8 weeks. Patients who manifested clinical progression during this period proceeded to receive standard of care. The primary endpoint was confirmed objective tumor response. A 2‐stage Fleming design was used such that if at most 1 confirmed partial response (PR) or complete response was observed in the first 20 patients (stage 1), the treatment would be considered ineffective, and further enrollment would be discontinued. RESULTS: Only 1 PR was observed in the first 20 patients. By the time of study closure, 5 additional patients who were already being screened for study inclusion were enrolled. Of the 25 patients (15 women, 10 men; 4 stage IIIB, 21 stage IV; median age, 67 years [range, 45‐85 years]), there were 3 (12%) PRs and 6 (24%) cases with stable disease observed. The median time‐to‐progression and progression‐free survival was 2.8 months. Seven (28%) patients remained progression‐free at 24 weeks. No grade 3 or higher hematologic adverse events were observed. Thirteen (52%) patients had a grade 3 nonhematologic adverse event, with fatigue (20%), diarrhea (8%), and dyspnea (8%) being the most common. CONCLUSIONS: Sorafenib is not effective as front‐line therapy in the general unselected NSCLC population. The window of opportunity design is feasible for estimating the activity of novel compounds. Cancer 2010. © 2010 American Cancer Society.