Valproic acid combined with cisplatin-based chemoradiation in locally advanced head and neck squamous cell carcinoma patients and associated biomarkers.

摘要: Background Cisplatin-based chemoradiation (CCRT) offers locally advanced head and neck squamous cell carcinoma (LAHNSCC) patients high local control rate, however, relapses are frequent. Our goal was to evaluate if association of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, with CCRT improved response rate (RR) associated biomarkers. Methods This phase II trial included unresectable (LA) oropharynx (OP) carcinoma. began after 2 weeks VPA (P1). Primary RR at 8 (CRT)+VPA (P2). Biomarkers microRNA (miR) polymerase chain reaction (PCR)-array profiling in plasma compared healthy controls by two-sample t-test. Distribution p-values analysed beta-uniform mixture. Findings were validated real-time PCR quantitative (qPCR) for selected miRs saliva. p16, HDAC2 RAD23 Homolog B, Nucleotide Excision Repair Protein (HR23B) tumour immunohistochemistry evaluated. Results Given significant toxicities, accrual interrupted inclusion ten LA p16 negative OP patients. All male, smokers/ex-smokers, aged 41-65 previous moderate/high alcohol intake. Nine evaluable yielded 88%. At false discovery 5%, 169 differentially expressed between controls, including lower expression suppressors (TSs) such as miR-31, -222, -let-7a/b/e -145. miR-let-7a/e qPCR using A H-score above 170 90% accurate predicting 6-month disease-free survival. Conclusions CRT offered RR; prohibitive which led early termination. Patients had distinct pattern miR expression, mainly low levels TS targeting Tumor protein P53 (TP53). reinforces the aggressive nature tumours (NCT01695122).