An international, multicenter phase II trial of bortezomib in patients with hepatocellular carcinoma

摘要: Background and Rationale Bortezomib (PS-341, VELCADE®) is a selective inhibitor of the 26S proteasome, an integral component ubiquitin-proteasome pathway. This phase II study evaluated activity tolerability bortezomib in unresectable hepatocellular carcinoma (HCC) patients. Methods The primary endpoint was confirmed tumor response rate (RR) with secondary endpoints including duration response, time to disease progression, survival toxicity. Treatment consisted bortezomib, 1.3 mg/m2 IV bolus on days 1, 4, 8, 11 each 21-day treatment cycle. Eligibility included: no prior systemic chemotherapy, ECOG PS 0-2, Child-Pugh A or B, preserved hematologic, hepatic neurologic function; liver-directed therapy permitted. Results Thirty-five patients enrolled received median 2 cycles (range 1–12). Overall, 24 4 had maximum severity grade 3 adverse events (AEs), respectively. No related deaths occurred. Only thrombocytopenia (11%) seen greater than 10% One patient achieved partial lasting 13 weeks during progressed 11.6 months later; two for 6 months. Median time-to-progression 1.6 months 6.0 months. Conclusions international, multicenter trial as monotherapy HCC And, despite lack significant activity, this report serves baseline clinical experience development future dual biologic approaches bortezomib.