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Phase II trial of Sorafenib in conjunction with chemotherapy and as maintenance therapy in extensive-stage small cell lung cancer

  • PHASE II STUDIES
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Summary

Objectives Sorafenib is a multi-tyrosine kinase inhibitor of Raf kinase, VEGFR, and PDGFR. Angiogenesis is important for growth and progression of SCLC. This trial was conducted to evaluate whether the combination of cisplatin and etoposide plus concurrent and sequential sorafenib could prolong survival in patients with previously untreated SCLC. Methods Previously untreated patients with extensive stage SCLC were treated with cisplatin and etoposide days 1, 2, 3 for four cycles, concurrent with sorafenib 200 mg orally bid starting day 1 cycle 1. Patients with no disease progression after four cycles continued sorafenib 400 mg orally bid as maintenance for maximum of 12 months. The primary endpoint was 1 year survival with response rate and safety as secondary endpoints. Results A total of 18 patients were enrolled with 17 evaluable patients. One patient had a complete response, seven patients had a partial response (overall response rate of 47 %) and one patient had stable disease. Overall median survival was 7.4 months and 1 year survival was 25 %. The most common treatment-related adverse events included fatigue, anorexia, rash, diarrhea, neutropenia and weight loss. Grade 5 GI bleeding, pulmonary hemorrhage and neutropenia occurred in one pt (6 %) each. Accrual was halted on the basis of safety profile as well as preliminary efficacy data. Conclusions The combination of platinum based chemotherapy and sorafenib has significant toxicity at current dose levels and is associated with disappointing efficacy data.

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Conflict of interest

Nathan A. Pennell received research funding from Genentech and served as a consultant for Boehringer Ingelheim and Oncogenex. Balazs Halmos received research funding from Daiichi Sankyo; Eli Lilly and Oncothyreon. All other authors declare no conflict of interest

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Authors and Affiliations

  1. University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA

    Neelesh Sharma & Afshin Dowlati

  2. Cleveland Clinic Taussig Cancer Institute, and Case Comprehensive Cancer Center, Cleveland, OH, USA

    Nathan Pennell, Patrick Ma & Tarek Mekhail

  3. New York-Presbyterian Hospital, Columbia University, New York, NY, USA

    Balazs Halmos

  4. Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Myles Nickolich, Pingfu Fu & Afshin Dowlati

  5. Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH, USA

    Neelesh Sharma

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  1. Neelesh Sharma
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Correspondence to Neelesh Sharma.

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Sharma, N., Pennell, N., Nickolich, M. et al. Phase II trial of Sorafenib in conjunction with chemotherapy and as maintenance therapy in extensive-stage small cell lung cancer. Invest New Drugs 32, 362–368 (2014). https://doi.org/10.1007/s10637-013-0061-6

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  • DOI: https://doi.org/10.1007/s10637-013-0061-6

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