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Randomized phase II trial of sorafenib alone or in combination with carboplatin/paclitaxel in women with recurrent platinum sensitive epithelial ovarian, peritoneal, or fallopian tube cancer

  • PHASE II STUDIES
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Summary

Background/Purpose This study was designed to evaluate the response and toxicity of sorafenib alone or when combined with carboplatin and paclitaxel in patients with platinum-sensitive, recurrent ovarian cancer, fallopian tube cancer, or primary peritoneal cancer (EOC). Methods Patients with recurrent platinum-sensitive EOC with no more than 2 prior courses of chemotherapy were randomized to single-agent sorafenib 400 mg twice daily or combination sorafenib 400 mg bid (days 2–19) with IV carboplatin (AUC 6) and IV paclitaxel 175 mg/m2 (S+C/T) every 3 weeks. Single agent sorafenib could cross over to combination upon progression. Results Patients were initially randomized to either arm, however, due to poor accrual, sorafenib arm was prematurely closed. A total of 13 patients were evaluable for response to sorafenib and 23 patients were evaluable for response to S+C/T. Objective response rate (RR) was 15 % for patients on sorafenib vs. 61 % for patients on S+C/T (p = 0.014); stable disease was seen in 62 % and 35 %, respectively. Clinical benefit rate (CBR) at 4 months (mos.) was 69 % for S and 65 % for S+C/T. The median progression free survival was 5.6 months on sorafenib vs. 16.8 months on S+C/T (p = 0.012) and there was no significant difference of overall survival between two arms (p = 0.974) with median overall survival 25.6 months under sorafenib vs. 25.9 months on S+C/T. Patients remained on trial for a median of 7.8 cycles on sorafenib and 5.4 cycles on S+C/T. Conclusion Sorafenib, alone or in combination with carboplatin and paclitaxel, has activity in patients with platinum-sensitive EOC. Sorafenib in combination with carboplatin and paclitaxel improved RR and PFS; however, there were increased grade and frequencies of toxicities.

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Acknowledgments

Supported by grant U01-CA62502 (PI: A. Dowlati) from the National Institutes of Health.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

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

    Anita Schwandt

  2. Obstetrics and Gynecology, Summa Akron City Hospital, Akron, OH, USA

    Vivian E. von Gruenigen

  3. H. Lee Moffitt Cancer Center, Tampa, FL, USA

    Robert M. Wenham

  4. Department of Obstetrics and Gynecology, University Hospitals Case Medical Center, Cleveland, OH, USA

    Heidi Frasure, Susan Eaton, Nancy Fusco & Steven Waggoner

  5. Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Heidi Frasure, Susan Eaton, Nancy Fusco & Steven Waggoner

  6. Case Comprehensive Cancer Center, Cleveland, OH, USA

    Pingfu Fu & Afshin Dowlati

  7. Cancer Therapeutics Evaluation Program, National Cancer Institute, Maryland, Bethesda, MD, USA

    John J. Wright

  8. Department of Obstetrics and Gynecology, University Hospitals Case Medical Center, Seidman Cancer Center, Mac 7128, 11100 Euclid Avenue, Cleveland, OH, 44106, USA

    Steven Waggoner

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  1. Anita Schwandt
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Correspondence to Steven Waggoner.

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Schwandt, A., von Gruenigen, V.E., Wenham, R.M. et al. Randomized phase II trial of sorafenib alone or in combination with carboplatin/paclitaxel in women with recurrent platinum sensitive epithelial ovarian, peritoneal, or fallopian tube cancer. Invest New Drugs 32, 729–738 (2014). https://doi.org/10.1007/s10637-014-0078-5

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  • DOI: https://doi.org/10.1007/s10637-014-0078-5

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