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Cancer Chemotherapy and Pharmacology

, Volume 66, Issue 1, pp 203–207 | Cite as

Sorafenib in combination with carboplatin and paclitaxel as neoadjuvant chemotherapy in patients with advanced ovarian cancer

  • Martin Pölcher
  • Meike Eckhardt
  • Christoph Coch
  • Matthias Wolfgarten
  • Kirsten Kübler
  • Gunther Hartmann
  • Walther Kuhn
  • Christian Rudlowski
Short Communication

Abstract

Purpose

Sorafenib is a novel oral anticancer agent targeting signal transduction and angiogenic pathways through inhibitory effects against MAP kinases and vascular endothelial growth factor receptor-2. The objectives of this neoadjuvant phase II-trial in patients with advanced epithelial ovarian cancer were to assess the activity and tolerability of the combination therapy of carboplatin/paclitaxel with multi-target tyrosine kinase inhibitor sorafenib.

Materials and methods

Patients with histologically proven stage IIIC or IV disease and large volume ascites were eligible. Enrolled patients received 2 of 6 cycles carboplatin (area under the curve 5) and paclitaxel (175 mg/m2) preoperatively and concomitant sorafenib 400 mg twice daily. After four cycles of postoperative chemotherapy, a maintenance phase of single agent oral sorafenib through 1 year was planned. This phase II-study was planned with a sample size of 102 patients and progression-free survival as primary study endpoint.

Results

Four patients were enrolled. After preoperative treatment and cytoreductive surgery, all patients were excluded from protocol due to severe toxicities. Three patients had life threatening events (cardiac output failure, myocardial infarction, anastomotic leak); two patients had primary progressive disease. The study was terminated on the basis of the recommendation of an independent data safety monitoring board.

Conclusion

The addition of sorafenib to carboplatin/paclitaxel chemotherapy was not feasible within this neoadjuvant regimen in primary advanced ovarian cancer. Although the occurrence of serious adverse events might have emerged at random, a detrimental effect of preoperative study medication could not be denied. Further evaluations of sorafenib in ovarian cancer are warranted.

Keywords

Sorafenib Ovarian cancer Neoadjuvant chemotherapy Carboplatin Paclitaxel 

Notes

Conflict of interest statement

Christian Rudlowski: Research Funding (Bayer HealthCare AG, Deutschland). All other authors indicated no potential conflict of interest.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Martin Pölcher
    • 1
  • Meike Eckhardt
    • 1
    • 2
  • Christoph Coch
    • 2
  • Matthias Wolfgarten
    • 1
  • Kirsten Kübler
    • 1
  • Gunther Hartmann
    • 2
  • Walther Kuhn
    • 1
  • Christian Rudlowski
    • 1
  1. 1.Department of Gynecology and Obstetrics, Center for Integrated Oncology, Bonn University Medical CenterUniversity Hospital of BonnBonnGermany
  2. 2.Institute of Clinical Chemistry and Pharmacology, Center for Integrated OncologyUniversity Hospital of BonnBonnGermany

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