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

  • PHASE II STUDIES
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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.

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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

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Acknowledgement

Supported by the Phase 2 Consortium Contract (NCI N01 CM17104).

Author information

Authors and Affiliations

  1. Mayo Clinic Florida, Jacksonville, FL, USA

    George P. Kim

  2. Mayo Clinic Rochester, Rochester, MN, USA

    Michelle R. Mahoney, Daniel Szydlo, Henry C. Pitot, Joseph Rubin & Charles Erlichman

  3. National University Hospital, Singapore, Singapore

    Tony S. K. Mok

  4. Mayo Clinic Arizona, Scottsdale, AZ, USA

    Robert Marshke

  5. University of Wisconsin Carbone Cancer Center, Madison, WI, USA

    Kyle Holen

  6. Washington University, St. Louis, MO, USA

    Joel Picus

  7. Royal Prince Alfred Hospital, Camperdown, Australia

    Michael Boyer

  8. Karmanos Cancer Institute, Detroit, MI, USA

    Philip A. Philip

  9. Sir Charles Gairdner Hospital, Perth, Australia

    Anna Nowak

  10. National Cancer Institute, Rockville, MD, USA

    John J. Wright

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  1. George P. Kim
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Correspondence to George P. Kim.

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Kim, G.P., Mahoney, M.R., Szydlo, D. et al. An international, multicenter phase II trial of bortezomib in patients with hepatocellular carcinoma. Invest New Drugs 30, 387–394 (2012). https://doi.org/10.1007/s10637-010-9532-1

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  • DOI: https://doi.org/10.1007/s10637-010-9532-1

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