TY - JOUR
T1 - An international, multicenter phase II trial of bortezomib in patients with hepatocellular carcinoma
AU - Kim, George P.
AU - Mahoney, Michelle R.
AU - Szydlo, Daniel
AU - Mok, Tony S.K.
AU - Marshke, Robert
AU - Holen, Kyle
AU - Picus, Joel
AU - Boyer, Michael
AU - Pitot, Henry C.
AU - Rubin, Joseph
AU - Philip, Philip A.
AU - Nowak, Anna
AU - Wright, John J.
AU - Erlichman, Charles
PY - 2012/2
Y1 - 2012/2
N2 - Background and Rationale Bortezomib (PS- 341, VELCADE®) is a selective inhibitor of the 26S proteasome, an integral component of the ubiquitinproteasome pathway. This phase II study evaluated the activity and tolerability of bortezomib in unresectable hepatocellular carcinoma (HCC) patients. Methods The primary endpoint was confirmed tumor response rate (RR) with secondary endpoints including duration of response, time to disease progression, survival and toxicity. Treatment consisted of bortezomib, 1.3 mg/m 2 IV bolus on days 1, 4, 8, and 11 of each 21-day treatment cycle. Eligibility included: no prior systemic chemotherapy, ECOG PS 0-2, Child-Pugh A or B, preserved hematologic, hepatic and neurologic function; prior liver-directed therapy was permitted. Results Thirty-five patients enrolled and received a median of 2 cycles of treatment (range 1-12). Overall, 24 and 4 patients had a maximum severity of grade 3 and 4 adverse events (AEs), respectively. No treatment related deaths occurred. Only thrombocytopenia (11%) was seen in greater than 10% of patients. One patient achieved a partial response, lasting 13 weeks during treatment and progressed 11.6 months later; two patients received treatment for greater than 6 months. Median time-to-progression was 1.6 months and median survival was 6.0 months. Conclusions This international, multicenter trial evaluated bortezomib as monotherapy in unresectable HCC patients. And, despite the lack of significant activity, this report serves as a baseline clinical experience for the development of future dual biologic approaches including bortezomib.
AB - Background and Rationale Bortezomib (PS- 341, VELCADE®) is a selective inhibitor of the 26S proteasome, an integral component of the ubiquitinproteasome pathway. This phase II study evaluated the activity and tolerability of bortezomib in unresectable hepatocellular carcinoma (HCC) patients. Methods The primary endpoint was confirmed tumor response rate (RR) with secondary endpoints including duration of response, time to disease progression, survival and toxicity. Treatment consisted of bortezomib, 1.3 mg/m 2 IV bolus on days 1, 4, 8, and 11 of each 21-day treatment cycle. Eligibility included: no prior systemic chemotherapy, ECOG PS 0-2, Child-Pugh A or B, preserved hematologic, hepatic and neurologic function; prior liver-directed therapy was permitted. Results Thirty-five patients enrolled and received a median of 2 cycles of treatment (range 1-12). Overall, 24 and 4 patients had a maximum severity of grade 3 and 4 adverse events (AEs), respectively. No treatment related deaths occurred. Only thrombocytopenia (11%) was seen in greater than 10% of patients. One patient achieved a partial response, lasting 13 weeks during treatment and progressed 11.6 months later; two patients received treatment for greater than 6 months. Median time-to-progression was 1.6 months and median survival was 6.0 months. Conclusions This international, multicenter trial evaluated bortezomib as monotherapy in unresectable HCC patients. And, despite the lack of significant activity, this report serves as a baseline clinical experience for the development of future dual biologic approaches including bortezomib.
KW - Antineoplastic agents
KW - Biologic agents
KW - Boronic acids
KW - Treatment outcome
UR - http://www.scopus.com/inward/record.url?scp=84856554756&partnerID=8YFLogxK
U2 - 10.1007/s10637-010-9532-1
DO - 10.1007/s10637-010-9532-1
M3 - Article
C2 - 20839030
AN - SCOPUS:84856554756
SN - 0167-6997
VL - 30
SP - 387
EP - 394
JO - Investigational New Drugs
JF - Investigational New Drugs
IS - 1
ER -