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Mitomycin C plus cisplatin for systemic treatment of recurrent BRCA1-associated ovarian cancer

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Summary

Background Previous studies on neoadjuvant therapy for BRCA1-driven ovarian cancer (OC) demonstrated higher efficacy of mitomycin C plus cisplatin combination as compared to standard drug schemes. These data call for evaluation of the utility of this regimen for the treatment of recurrent BRCA1-associated OC. Methods The study included 12 BRCA1 germ-line mutation carriers, whose disease relapsed after one (n = 4) or two (n = 8) lines of chemotherapy. The patients received cisplatin 100 mg/m2 and mitomycin C 10 mg/m2, given every four weeks, for 6 (n = 10), 8 (n = 1) or 5 (n = 1) cycles. Retrospective data on conventional treatment of OC relapses in BRCA1 heterozygotes (n = 47) served as a control. Results Grade 3–4 toxicities were observed in 4/12 (33%) cases. There were 6 complete responses (CR), 4 partial responses (PR) and 2 instances of stable disease (SD). Comparison of patients receiving mitomycin C plus cisplatin (n = 4) or conventional therapy (n = 44) at first relapse demonstrated marginal improvement of the progression-free survival (PFS) (16.6 months vs. 10.2 months, P = .067). Use of mitomycin C plus cisplatin (n = 8) for the treatment of second relapse resulted in significant prolongation of PFS as compared to standard regimens (n = 31) (14.8 months vs. 4.8 months, P = .002). Conclusions Mitomycin C plus cisplatin shows promising activity in recurrent BRCA1-driven ovarian cancer.

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Acknowledgements

We are cordially thankful to Ms. Sophie Leonard for the editing of this manuscript.

Funding

This work has been supported by the Russian Science Foundation [grant number 19-75-10062].

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Authors and Affiliations

  1. N.N. Petrov National Medical Research Center of Oncology, Leningradskaya, 68, Pesochny-2, 197758, St.-Petersburg, Russia

    Tatyana V. Gorodnova, Anna P. Sokolenko, Sergey V. Kondratiev, Khristina B. Kotiv, Alexey M. Belyaev, Igor V. Berlev & Evgeny N. Imyanitov

  2. St.-Petersburg Pediatric Medical University, 194100, St.-Petersburg, Russia

    Anna P. Sokolenko & Evgeny N. Imyanitov

  3. I.I. Mechnikov North-Western Medical University, 191015, St.-Petersburg, Russia

    Evgeny N. Imyanitov

Authors
  1. Tatyana V. Gorodnova
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  2. Anna P. Sokolenko
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  3. Sergey V. Kondratiev
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  4. Khristina B. Kotiv
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  5. Alexey M. Belyaev
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  6. Igor V. Berlev
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  7. Evgeny N. Imyanitov
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Contributions

Conceptualization: Tatyana V. Gorodnova, Evgeny N. Imyanitov.

Methodology: Tatyana V. Gorodnova, Anna P. Sokolenko, Evgeny N. Imyanitov.

Formal analysis and investigation: Tatiana V. Gorodnova, Sergey V. Kondratiev, Khristina B. Kotiv, Alexey M. Belyaev, Igor. V. Berlev.

Writing – original draft preparation: Anna P. Sokolenko, Evgeny N. Imyanitov.

Writing – review and editing: all authors.

Funding acquisition: Khristina B. Kotiv.

Corresponding author

Correspondence to Anna P. Sokolenko.

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Conflict of interest

Tatyana V. Gorodnova, Anna P. Sokolenko, Sergey V. Kondratiev, Khristina B. Kotiv, Alexey M. Belyaev, Igor V. Berlev, and Evgeny N. Imyanitov declare that they have no conflicts of interest.

Ethical approval

The study was approved by the local Ethics Committee. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

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All patients provided written informed consent.

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Gorodnova, T.V., Sokolenko, A.P., Kondratiev, S.V. et al. Mitomycin C plus cisplatin for systemic treatment of recurrent BRCA1-associated ovarian cancer. Invest New Drugs 38, 1872–1878 (2020). https://doi.org/10.1007/s10637-020-00965-8

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  • DOI: https://doi.org/10.1007/s10637-020-00965-8

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