Investigational New Drugs

, Volume 30, Issue 1, pp 387–394

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

Authors

    • Mayo Clinic Florida
  • Michelle R. Mahoney
    • Mayo Clinic Rochester
  • Daniel Szydlo
    • Mayo Clinic Rochester
  • Tony S. K. Mok
    • National University Hospital
  • Robert Marshke
    • Mayo Clinic Arizona
  • Kyle Holen
    • University of Wisconsin Carbone Cancer Center
  • Joel Picus
    • Washington University
  • Michael Boyer
    • Royal Prince Alfred Hospital
  • Henry C. Pitot
    • Mayo Clinic Rochester
  • Joseph Rubin
    • Mayo Clinic Rochester
  • Philip A. Philip
    • Karmanos Cancer Institute
  • Anna Nowak
    • Sir Charles Gairdner Hospital
  • John J. Wright
    • National Cancer Institute
  • Charles Erlichman
    • Mayo Clinic Rochester
PHASE II STUDIES

DOI: 10.1007/s10637-010-9532-1

Cite this article as:
Kim, G.P., Mahoney, M.R., Szydlo, D. et al. Invest New Drugs (2012) 30: 387. doi:10.1007/s10637-010-9532-1

Summary

Background and Rationale Bortezomib (PS-341, VELCADE®) is a selective inhibitor of the 26S proteasome, an integral component of the ubiquitin-proteasome 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/m2 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.

Keywords

Boronic acidsAntineoplastic agentsBiologic agentsTreatment outcome

Abbreviations

HCC

Hepatocellular carcinoma

RR

Response rate

AEs

Adverse events

VEGF

Vascular endothelial growth factor

UNL

Upper normal limit

CTCAE

Common terminology criteria for adverse events

CBCs

Complete blood cell counts

CR

Complete response

PR

Partial response

PD

Progressive disease

SD

Stable disease

CIs

Confidence intervals

SHARP

Sorafenib hepatocellular carcinoma assessment randomized protocol

Copyright information

© Springer Science+Business Media, LLC 2010