A phase II trial of sorafenib and dacarbazine for leiomyosarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumors Journal Article


Authors: D'Adamo, D. R.; Dickson, M. A.; Keohan, M. L.; Carvajal, R. D.; Hensley, M. L.; Hirst, C. M.; Ezeoke, M. O.; Ahn, L.; Qin, L. X.; Antonescu, C. R.; Lefkowitz, R. A.; Maki, R. G.; Schwartz, G. K.; Tap, W. D.
Article Title: A phase II trial of sorafenib and dacarbazine for leiomyosarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumors
Abstract: Background: Sorafenib and dacarbazine have low single-agent response rates in metastatic sarcomas. As angiogenesis inhibitors can enhance the efficacy of chemotherapy, we investigated the combination of sorafenib and dacarbazine in select sarcoma subtypes. Materials and Methods: Patients with leiomyosarcoma (LMS), synovial sarcoma (SS), or malignant peripheral nerve sheath tumors (MPNST) with up to two previous lines of therapy and adequate hepatic, renal, and marrow function received 3-week cycles of sorafenib at 400 mg oral twice daily and dacarbazine 1,000 mg/m2 intravenously (later reduced to 850 mg/m2). Patients were evaluated for response every 6 weeks. The primary objective was to determine the disease control rate (DCR) of sorafenib plus dacarbazine in the selected sarcoma subtypes. Results: The study included 37 patients (19 female); median age was 55 years (range 26–87); and histologies included LMS (22), SS (11), and MPNST (4). The DCR was 46% (17/37). Median progression-free survival was 13.4 weeks. The RECIST response rate was 14% (5/37). The Choi response rate was 51% (19/37). Median overall survival was 13.2 months. Of the first 25 patients, 15 (60%) required dacarbazine dose reductions for hematologic toxicity, with one episode of grade 5 neutropenic fever. After reducing the starting dose of dacarbazine to 850 mg/m2, only 3 of the final 12 (25%) patients required dose reduction. Conclusion: This phase II study met its primary endpoint with an 18-week DCR of 46%. The clinical activity of dacarbazine plus sorafenib in patients with these diagnoses is modest. Implications for Practice: Metastatic soft tissue sarcomas are a heterogeneous group of relatively rare malignancies. Most patients are treated with cytotoxic chemotherapy or targeted therapy in the form of tyrosine kinase inhibitors. Response rates are relatively low, and there is a need for better therapies. This clinical trial demonstrates that combining a cytotoxic therapy (dacarbazine) with an antiangiogenic small molecule (sorafenib) is feasible and associated with favorable disease-control rates; however, it also increases the potential for significant toxicity. © AlphaMed Press 2018
Keywords: chemotherapy; angiogenesis; soft tissue sarcoma; phase ii clinical trials
Journal Title: The Oncologist
Volume: 24
Issue: 6
ISSN: 1083-7159
Publisher: Oxford University Press  
Date Published: 2019-06-01
Start Page: 857
End Page: 863
Language: English
DOI: 10.1634/theoncologist.2018-0160
PROVIDER: scopus
PUBMED: 30126857
PMCID: PMC6656505
DOI/URL:
Notes: Article -- Export Date: 1 July 2019 -- Source: Scopus
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MSK Authors
  1. Cristina R Antonescu
    895 Antonescu
  2. Li-Xuan Qin
    191 Qin
  3. Mary Louise Keohan
    125 Keohan
  4. Martee L Hensley
    290 Hensley
  5. Linda Su Hyun Ahn
    25 Ahn
  6. Mark Andrew Dickson
    170 Dickson
  7. William Douglas Tap
    374 Tap
  8. Catherine Mackensie Hirst
    4 Hirst
  9. Marietta Ogochukwu Ezeoke
    6 Ezeoke