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Originally published as JCO Early Release 10.1200/JCO.2008.20.4495 on May 18 2009 © 2009 American Society of Clinical Oncology.
Phase II Study of Sorafenib in Patients With Metastatic or Recurrent SarcomasFrom the Departments of Medicine, Pathology, Radiology, and Biostatistics and Epidemiology, Memorial Sloan-Kettering Cancer Center; Rockefeller University, New York, NY; Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI; Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago; Evanston Northwestern Health Care, Evanston, IL; Carolinas Hematology-Oncology and University of North Carolina, Charlotte, NC; Division of Hematology and Oncology, University Hospitals Case Medical Center, Case Comprehensive Cancer Center, Cleveland, OH; Institute for Drug Development, Cancer Therapy and Research Center at the University of Texas Health Science Center, San Antonio, TX; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC; and the University of Colorado Cancer Center, Aurora, CO. Corresponding author: Robert G. Maki, MD, PhD, Melanoma-Sarcoma Program, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Howard 909, New York, NY 10065; e-mail: makir{at}mskcc.org. Purpose Since activity of sorafenib was observed in sarcoma patients in a phase I study, we performed a multicenter phase II study of daily oral sorafenib in patients with recurrent or metastatic sarcoma. Patients and Methods We employed a multiarm study design, each representing a sarcoma subtype with its own Simon optimal two-stage design. In each arm, 12 patients who received 0 to 1 prior lines of therapy were treated (0 to 3 for angiosarcoma and malignant peripheral-nerve sheath tumor). If at least one Response Evaluation Criteria in Solid Tumors (RECIST) was observed, 25 further patients with that sarcoma subtype were accrued. Results Between October 2005 and November 2007, 145 patients were treated; 144 were eligible for toxicity and 122 for response. Median age was 55 years; female-male ratio was 1.8:1. The median number of cycles was 3. Five of 37 patients with angiosarcoma had a partial response (response rate, 14%). This was the only arm to meet the RECIST response rate primary end point. Median progression-free survival was 3.2 months; median overall survival was 14.3 months. Adverse events (typically dermatological) necessitated dose reduction for 61% of patients. Statistical modeling in this limited patient cohort indicated sorafenib toxicity was correlated inversely to patient height. There was no correlation between phosphorylated extracellular signal regulated kinase expression and response in six patients with angiosarcoma with paired pre- and post-therapy biopsies. Conclusion As a single agent, sorafenib has activity against angiosarcoma and minimal activity against other sarcomas. Further evaluation of sorafenib in these and possibly other sarcoma subtypes appears warranted, presumably in combination with cytotoxic or kinase-specific agents. Supported by the National Cancer Institute (NCI) Program Project Grant No. CA47179, NCI phase II contract CM62202, Cycle for Survival, the Shuman Family Fund for GIST research, and the Sarcoma Research Fund. Presented in part in oral format at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL. Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article. Clinical Trials repository link available JCO.org. Clinical trial information can be found for the following: NCT00245102 [ClinicalTrials.gov] .
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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