Mitomycin C plus cisplatin for systemic treatment of recurrent BRCA1 -associated ovarian cancer
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PHASE II STUDIES
Mitomycin C plus cisplatin for systemic treatment of recurrent BRCA1-associated ovarian cancer Tatyana V. Gorodnova 1 & Anna P. Sokolenko 1,2 Igor V. Berlev 1 & Evgeny N. Imyanitov 1,2,3
&
Sergey V. Kondratiev 1 & Khristina B. Kotiv 1 & Alexey M. Belyaev 1 &
Received: 21 May 2020 / Accepted: 16 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords BRCA1 mutation . Mitomycin C plus cisplatin . Ovarian cancer . Recurrence
Introduction Ovarian cancer (OC) is a common oncological disease among women with a life-time risk approaching approximately 1:70. OC rarely causes symptoms at the early stages of tumor development and cannot be reliably detected by available screening tools. As a consequence, Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10637-020-00965-8) contains supplementary material, which is available to authorized users. * Anna P. Sokolenko [email protected] 1
N.N. Petrov National Medical Research Center of Oncology, Leningradskaya, 68, Pesochny-2, 197758 St.-Petersburg, Russia
2
St.-Petersburg Pediatric Medical University, 194100 St.-Petersburg, Russia
3
I.I. Mechnikov North-Western Medical University, 191015 St.-Petersburg, Russia
most newly diagnosed OC cases are characterized by metastatic spread and require extensive surgical intervention and systemic therapy, which aim to reduce tumor burden. Almost all OCs eventually relapse after initially successful treatment; therefore, the improvement of the management of OC recurrences is of high medical importance [1–4]. Approximately 10–20% of OC mor
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