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Carboplatin re-treatment in platinum-resistant epithelial ovarian cancer patients

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Abstract

Purpose

Treatment of multi-resistant epithelial ovarian cancer represents a clinical challenge with limited choices. Anti-angiogenic therapy has shown great potential in combination with frontline-therapy. Studies investigating heavily pre-treated patients are few. This study investigated the effect of re-treating patients with carboplatin combined with bevacizumab and cell-free DNA (cfDNA) as a potential predictor of outcome.

Methods

This single-center study enrolled 73 multi-resistant ovarian cancer patients from 2008 to 2015. Patients were treated with a combination of bevacizumab (10 mg/kg) and carboplatin (AUC5) every 3 weeks. Baseline plasma samples were analyzed for cfDNA levels. Treatment response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria and CA125 blood values.

Results

The response rate according to RECIST and/or CA125 was 57%. Median number of cycles was 6. The median progression-free survival and overall survival was 5.0 and 11.2 months, respectively. Eighteen patients developed allergic reactions to carboplatin. Patients were grouped into two cfDNA-groups according to median value. The cfDNA value was correlated to progression-free survival (PFS, p = 0.015), but not to overall survival (OS, p = 0.067) in the univariate analysis. In the multivariate analysis both PFS and OS were highly correlated to the levels of cfDNA (PFS, hazard ratio = 1.87, p = 0.012; OS, hazard ratio = 1.67, p = 0.037) with patients with high levels of cfDNA having poorest outcome.

Conclusion

Our results might provide guidance in cases with heavily pre-treated patients, where alternatives are limited. Carboplatin and bevacizumab treatment should be weighed against best supportive care, current non-platinum therapies and experimental treatment. cfDNA seems to offer prognostic insight.

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Acknowledgements

The authors would like to thank the staff at the Department of Oncology, Lillebaelt Hospital, who included patients and provided follow-up-data. A special thanks to Jette Leonhardt Hansen for data-registration and Karin Larsen for proofreading the manuscript. The authors would also like to thank technicians Tina Brandt Christensen, Lone Hartmann Hansen and Pia Nielsen for technical assistance.

Funding

The study was entirely funded by the Department of Oncology, Lillebaelt Hospital – University Hospital of Southern Denmark.

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Authors and Affiliations

  1. Department of Oncology, Lillebaelt Hospital – University Hospital of Southern Denmark,, Beriderbakken 4, 7100, Vejle, Denmark

    Mads Kingo Guldberg Hansen, Parvin Adimi, Anders Jakobsen & Karina Dahl Steffensen

  2. Department of Clinical Genetics, Lillebaelt Hospital – University Hospital of Southern Denmark, Beriderbakken 4, 7100, Vejle, Denmark

    Maja Patricia Smerdel

  3. Department of Pathology, Lillebaelt Hospital – University Hospital of Southern Denmark, Beriderbakken 4, 7100, Vejle, Denmark

    Marianne Waldstrøm

  4. Department of Clinical Biochemistry, Lillebaelt Hospital – University Hospital of Southern Denmark, Beriderbakken 4, 7100, Vejle, Denmark

    Rikke Fredslund Andersen

Authors
  1. Mads Kingo Guldberg Hansen
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  2. Maja Patricia Smerdel
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  3. Marianne Waldstrøm
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  4. Rikke Fredslund Andersen
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  5. Parvin Adimi
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  6. Anders Jakobsen
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  7. Karina Dahl Steffensen
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Contributions

Conception and design: MPS, AJ, KDS. Collection and assembly of data: MKGH, MPS, MW, RFA, PA, AJ, KDS. Data analysis and interpretation: MKGH, KDS. Manuscript writing: All authors. Final approval of manuscript: All authors. Accountable for all aspects of the work: All authors.

Corresponding author

Correspondence to Mads Kingo Guldberg Hansen.

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Conflict of interest

None declared.

Ethics approval

The study was conducted in accordance with the Helsinki II Declaration and approved by The Regional Committee on Health Research Ethics for Southern Denmark (S-20080033) and The Data Protection Agency. Information on the patients was treated in accordance with the Danish act on Processing of Personal Data.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

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All authors have approved the manuscript and consent for publication.

Availability of data and material

Not applicable. Database closed down according to Danish law.

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Hansen, M.K.G., Smerdel, M.P., Waldstrøm, M. et al. Carboplatin re-treatment in platinum-resistant epithelial ovarian cancer patients. Cancer Chemother Pharmacol 86, 751–759 (2020). https://doi.org/10.1007/s00280-020-04162-5

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  • DOI: https://doi.org/10.1007/s00280-020-04162-5

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