DNA methyltransferase inhibitor guadecitabine combined with cisplatin and gemcitabine chemotherapy (SPIRE): Randomized expansion phase as neoadjuvant therapy for bladder urothelial carcinoma.

447 Background: Pre-clinical data support a hypothesis that DNA methyltransferase inhibition will circumvent cisplatin resistance in various cancers including urothelial carcinoma (UC). SPIRE comprised a previously reported phase Ib dose escalation phase for incurable metastatic solid cancers which established a recommended phase II dose (RP2D) for guadecitabine combined with gemcitabine and cisplatin (GC) chemotherapy (Crabb et al, ESMO...