Article Text
Abstract
Late-stage ovarian carcinoma is almost universally fatal. BRCA mutations are associated with an improved outcome and enhanced sensitivity to platinum chemotherapy, yet recurrence and platinum resistance remain a major problem and highly effective regimens following platinum failure do not yet exist. Here we report a remarkable case of cure following platinum-resistant stage III ovarian carcinoma in a woman with a BRCA2 mutation. The patient was subsequently treated with oral melphalan therapy and has not recurred in over 25 years. Melphalan is a bifunctional alkylator that creates inter- and intra-strand DNA cross-links. In a pharmaceutical screen, melphalan was shown to be selectively toxic to BRCA2-deficient breast cancer cell lines and produced a longer relapse-free survival in mice than did cisplatin or olaparib. There is increasing evidence to consider BRCA mutation status when selecting chemotherapy regimens, and melphalan treatment for BRCA-related ovarian cancer merits further investigation. Focusing attention on long-term survivors may provide new mechanistic insights into the biology of chemo-responsiveness.
- Chemotherapy
- cancer genetics
- carcinoma
- familial cancers
- gynaecological pathology
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Footnotes
Funding This work was funded by a Marsha Rivkin Center for Ovarian Cancer Research Grant (WDF) and both the McGill Centre for Experimental Therapeutics in Cancer and the McGill Integrated Cancer Research Training Program (DO). The funding sources had no role in the study design, collection, analysis or interpretation of data, nor in the writing of the report or decision to submit the paper for publication.
Competing interests None.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the Institutional Review Board at McGill University's Faculty of Medicine (Dr. Serge Gauthier, Chair of IRB).
Provenance and peer review Not commissioned; externally peer reviewed.