Overcoming Platinum Resistance Through the Use of a Copper-Lowering Agent

Menée sur 5 patientes atteintes d'un cancer ovarien de haut grade résistant aux sels de platine, cette étude évalue l'intérêt du trientine, un chélateur du cuivre, pour restaurer la sensibilité des tumeurs aux sels de platine

Résumé en anglais

Low levels of human copper transporter 1 (hCtr1) mRNA are associated with a shorter progression-free survival after platinum-based therapy. Pretreatment with a copper-lowering agent such as trientine enhanced hCtr1-mediated platinum uptake. Therefore, we conducted a pilot study (NCT01178112) of carboplatin and trientine with the goal of resensitizing advanced cancer patients to platinum chemotherapy. This case report reviews the outcomes of five patients with platinum-resistant high-grade epithelial ovarian cancer enrolled on the study to date. Overall, they tolerated treatment well. Severe adverse events that occurred in two patients were myelosuppression, notably anemia requiring transfusion. Dose-limiting toxicity was not observed within the first 28 days (cycle 1). After two cycles of therapy, partial remission was achieved in one patient (10+ months), stable disease in three patients (2, 3.5+ and 5 months, respectively), and one patient had progressive disease. These cases provide preliminary clinical evidence that the role of decreasing copper levels in reversing platinum resistance merits additional clinical investigation. Evaluation of this novel strategy is warranted in larger studies to assess the efficacy of this approach for treating platinum-resistant advanced epithelial ovarian cancer in patients with high copper levels.