PMID- 20839030
OWN - NLM
STAT- MEDLINE
DCOM- 20120508
LR  - 20211020
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Print)
IS  - 0167-6997 (Linking)
VI  - 30
IP  - 1
DP  - 2012 Feb
TI  - An international, multicenter phase II trial of bortezomib in patients with 
      hepatocellular carcinoma.
PG  - 387-94
LID - 10.1007/s10637-010-9532-1 [doi]
AB  - BACKGROUND AND RATIONALE: Bortezomib (PS-341, VELCADE(R)) 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.
FAU - Kim, George P
AU  - Kim GP
AD  - Mayo Clinic Florida, Jacksonville, FL, USA. kim.george@mayo.edu
FAU - Mahoney, Michelle R
AU  - Mahoney MR
FAU - Szydlo, Daniel
AU  - Szydlo D
FAU - Mok, Tony S K
AU  - Mok TS
FAU - Marshke, Robert
AU  - Marshke R
FAU - Holen, Kyle
AU  - Holen K
FAU - Picus, Joel
AU  - Picus J
FAU - Boyer, Michael
AU  - Boyer M
FAU - Pitot, Henry C
AU  - Pitot HC
FAU - Rubin, Joseph
AU  - Rubin J
FAU - Philip, Philip A
AU  - Philip PA
FAU - Nowak, Anna
AU  - Nowak A
FAU - Wright, John J
AU  - Wright JJ
FAU - Erlichman, Charles
AU  - Erlichman C
LA  - eng
GR  - N01 CM062205/CM/NCI NIH HHS/United States
GR  - N01 CM17104/CM/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
DEP - 20100914
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Boronic Acids)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Proteasome Inhibitors)
RN  - 0 (Pyrazines)
RN  - 69G8BD63PP (Bortezomib)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - EC 3.4.99.- (ATP dependent 26S protease)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Asia
MH  - Boronic Acids/administration & dosage/adverse effects/*therapeutic use
MH  - Bortezomib
MH  - Carcinoma, Hepatocellular/*drug therapy/metabolism/mortality/pathology
MH  - Disease-Free Survival
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Liver Neoplasms/*drug therapy/metabolism/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - North America
MH  - Protease Inhibitors/administration & dosage/adverse effects/*therapeutic use
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - *Proteasome Inhibitors
MH  - Pyrazines/administration & dosage/adverse effects/*therapeutic use
MH  - Time Factors
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC3896232
MID - NIHMS519807
EDAT- 2010/09/15 06:00
MHDA- 2012/05/09 06:00
PMCR- 2014/01/20
CRDT- 2010/09/15 06:00
PHST- 2010/08/04 00:00 [received]
PHST- 2010/08/24 00:00 [accepted]
PHST- 2010/09/15 06:00 [entrez]
PHST- 2010/09/15 06:00 [pubmed]
PHST- 2012/05/09 06:00 [medline]
PHST- 2014/01/20 00:00 [pmc-release]
AID - 10.1007/s10637-010-9532-1 [doi]
PST - ppublish
SO  - Invest New Drugs. 2012 Feb;30(1):387-94. doi: 10.1007/s10637-010-9532-1. Epub 
      2010 Sep 14.