Phase I dose escalation study of pan-histone deacetylase (HDAC) inhibitor abexinostat in combination with cisplatin in patients with advanced non-keratinizing nasopharyngeal carcinoma.

Abstract

e17059 Background: Non-keratinizing nasopharyngeal carcinoma (NPC) is associated with the Epstein-Barr Virus (EBV), and sensitive to chemotherapy and radiotherapy. Cisplatin-based combination therapy is the most effective treatment for metastatic NPC. Abexinostat, a pan-HDAC inhibitor, exhibited synergistic effects in combination with cisplatin in NPC tumor cell lines, either EBV-positive or negative. A phase I dose-escalation study was performed to determine the maximal tolerated dose, dose-limiting toxicities (DLTs) of abexinostat with a fixed dose of cisplatin in patients with relapsed or refractory advanced NPC. Methods: Abexinostat was administered BID on days 1-4 and 8-11 of a 21-day cycles. Cisplatin dose (75mg/m2) was given on day 3. Abexinostat treatment started 2 days before to induce biological modifications in tumor cells prior to chemotherapy to maximize the synergistic effect. Since toxicities related to cisplatin are cumulative, dose-dependent and may be irreversible, the combination was li...