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Addition of vandetanib to pegylated liposomal doxorubicin (PLD) in patients with recurrent ovarian cancer. A randomized phase I/II study of the AGO Study Group (AGO-OVAR 2.13)

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Summary

Background PLD is a standard treatment in patients with recurrent platinum-resistant or refractory ovarian cancer. Vandetanib is an oral once daily administered inhibitor of VEGFR-, EGFR- and RET-signaling with activity in combination with chemotherapy in some solid tumours. We aimed to establish a feasible combination therapy of PLD and vandetanib in ovarian cancer. Methods Eligible patients were treated with PLD 50 mg/m2 q28 and vandetanib 100 mg/d po. It was planned to recruit at least 10 patients evaluable for toxicity over 2 treatment cycles. Primary endpoints were tolerability and safety; secondary endpoint was efficacy. Results Fourteen of 15 registered patients started treatment and were evaluable for toxicity. Three patients (21 %) stopped after first cycle (PD, withdrawal of consent, nausea/vomiting). The remaining 11 patients were treated for at least 2 cycles. Dose reductions of PLD and vandetanib were indicated in 4 (29 %) and 5 patients (36 %), respectively. The following G3/4 toxicities occurred per patient: 2 (14 %) elevated liver enzymes G3, 2 (14 %) neutropenia G3/4, 5 (36 %) PPE G3/4, 2 (14 %) mucositis G3. Tyrosine kinase inhibitor attributed side effects like hypertension or bowel perforations were not reported. Toxicity led to cessation of treatment in 4 patients (29 %). Ten patients were evaluable for response: PR 1, SD 4. The median PFS was 6.7 months and median OS was 11.1 months. Conclusions The combination of PLD 50 mg/m2q28 and vandetanib 100 mg/d is feasible, but may be intolerable due to reported toxicity.

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Acknowledgment

The authors would like to thank Peter Langmuir, Helmut Brasch, and Manfred Klevesath who represented Astra Zeneca at Data Safety Monitoring Board (representatives from AGO were PH, JR & AdB). We would like to thank Carmen Schade-Brittinger and her team from Coordination Center for Clinical trials for statistics, Peter Schantl and his team for monitoring, Christina Richter from AGO Study Office, and Silke Zaun from Astra Zeneca. Furthermore, we would like to thank the following investigators for their support of this study: Martina Reuss (Wiesbaden), Radoslav Chekerov (Berlin), Pauline Wimberger (Essen), Moritz Kanzow (Kiel), and Nikolaus de Gregorio (Ulm).

This study was funded by Astra Zeneca GmbH.

Ethical standards

This study complies with the current law of the country in which it was performed,

Potential conflicts of interest

P Harter: research grants and honoraria for lectures/consultation from Astra Zeneca. F Hilpert, A du Bois: honoraria for lectures/advisory boards from Astra Zeneca. R Kimmig: honoraria for lectures. G Elser, C. Kurzeder, J. Rau, J. Sehouli: none

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Authors and Affiliations

  1. Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Henricistr. 92, 45136, Essen, Germany

    Philipp Harter, Christian Kurzeder & Andreas du Bois

  2. Department of Gynecology and Gynecologic Oncology, HSK, Dr. Horst Schmidt Klinik, Wiesbaden, Germany

    Philipp Harter & Andreas du Bois

  3. Department of Gynecology, Campus Virchow-Klinikum, Charité Universitätsmedizin Berlin, Berlin, Germany

    Jalid Sehouli

  4. Department of Gynecology & Obstetrics, University Duisburg-Essen, Essen, Germany

    Rainer Kimmig

  5. Coordinating Center of Clinical Trials, Philips-University Marburg, Marburg, Germany

    Jörn Rau

  6. Department of Gynecology & Obstetrics, University Schleswig Holstein, Campus Kiel, Kiel, Germany

    Felix Hilpert

  7. Department of Gynecology & Obstetrics, University Ulm, Ulm, Germany

    Christian Kurzeder

  8. AGO Study Group, Wiesbaden, Germany

    Gabriele Elser

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  1. Philipp Harter
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  8. Andreas du Bois
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Correspondence to Philipp Harter.

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Harter, P., Sehouli, J., Kimmig, R. et al. Addition of vandetanib to pegylated liposomal doxorubicin (PLD) in patients with recurrent ovarian cancer. A randomized phase I/II study of the AGO Study Group (AGO-OVAR 2.13). Invest New Drugs 31, 1499–1504 (2013). https://doi.org/10.1007/s10637-013-0011-3

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  • DOI: https://doi.org/10.1007/s10637-013-0011-3

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