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Investigational New Drugs

, Volume 32, Issue 4, pp 729–738 | Cite as

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

  • Anita Schwandt
  • Vivian E. von Gruenigen
  • Robert M. Wenham
  • Heidi Frasure
  • Susan Eaton
  • Nancy Fusco
  • Pingfu Fu
  • John J. Wright
  • Afshin Dowlati
  • Steven WaggonerEmail author
PHASE II STUDIES

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.

Keywords

Sorafenib Ovarian cancer Gynecologic malignancies Chemotherapy Tyrosine kinase inhibitors (TKI) Molecular targeted agents (MTA) 

Notes

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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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Anita Schwandt
    • 1
  • Vivian E. von Gruenigen
    • 2
  • Robert M. Wenham
    • 3
  • Heidi Frasure
    • 4
    • 5
  • Susan Eaton
    • 4
    • 5
  • Nancy Fusco
    • 4
    • 5
  • Pingfu Fu
    • 6
  • John J. Wright
    • 7
  • Afshin Dowlati
    • 6
  • Steven Waggoner
    • 4
    • 5
    • 8
    Email author
  1. 1.Case Western Reserve University School of MedicineClevelandUSA
  2. 2.Obstetrics and GynecologySumma Akron City HospitalAkronUSA
  3. 3.H. Lee Moffitt Cancer CenterTampaUSA
  4. 4.Department of Obstetrics and GynecologyUniversity Hospitals Case Medical CenterClevelandUSA
  5. 5.Department of Reproductive BiologyCase Western Reserve University School of MedicineClevelandUSA
  6. 6.Case Comprehensive Cancer CenterClevelandUSA
  7. 7.Cancer Therapeutics Evaluation ProgramNational Cancer Institute, MarylandBethesdaUSA
  8. 8.Department of Obstetrics and GynecologyUniversity Hospitals Case Medical Center, Seidman Cancer CenterClevelandUSA

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