apatorsen and Carcinoma--Transitional-Cell

A randomised study to assess the addition of apatorsen, an antisense oligonucleotide that inhibits Hsp27 expression, to docetaxel in patients with metastatic urothelial carcinoma (mUC) relapsed after prior platinum-based chemotherapy.. Patients randomised to A/D (n = 99) had improved OS compared to docetaxel alone (n = 101): HR: 0.80, 80% CI: 0.65-0.98, P = 0.0784, median 6.4 vs 5.9 months. PFS and ORR were similar in both arms. A/D had more incidence of sepsis and urinary tract infections. Patients with baseline Hsp27 levels <5.7 ng/mL had improved OS compared to those with levels ≥5.7 ng/mL. Patients with a decline or ≤20.5% increase in Hsp27 from baseline benefited more from A/D than those with >20.5% increase.. A/D met its predefined OS end point in patients with platinum-refractory mUC in this phase II trial. This trial is hypothesis generating requiring further study before informing practice.

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Docetaxel; Down-Regulation; Drug Administration Schedule; Female; Gene Expression Regulation, Neoplastic; Heat-Shock Proteins; HSP27 Heat-Shock Proteins; Humans; Male; Middle Aged; Molecular Chaperones; Oligonucleotides; Recurrence; Survival Analysis; Treatment Outcome; Urologic Neoplasms