PMID- 14716767
OWN - NLM
STAT- MEDLINE
DCOM- 20040130
LR  - 20120625
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 100
IP  - 2
DP  - 2004 Jan 15
TI  - A Phase II trial of aprinocarsen, an antisense oligonucleotide inhibitor of 
      protein kinase C alpha, administered as a 21-day infusion to patients with 
      advanced ovarian carcinoma.
PG  - 321-6
AB  - BACKGROUND: It has been postulated that protein kinase C alpha (PKC-alpha) plays 
      a pivotal role in signal transduction in tumor cancer cells. Aprinocarsen, a 
      20-base antisense oligonucleotide, has shown ability to inhibit PKC-alpha protein 
      expression and inhibit tumor growth in human xenograft models. In a previous 
      Phase I trial, the authors demonstrated the safety and some evidence of activity 
      in ovarian carcinoma of aprinocarsen administered as a 21-day, continuous, 
      intravenous infusion. METHODS: In this Phase II trial, 36 patients with advanced 
      ovarian carcinoma were treated with aprinocarsen at a dose of 2 mg/kg per day 
      delivered as a 21-day, continuous, intravenous infusion. The primary objective 
      was to determine the antitumor response, and the secondary objectives were to 
      evaluate toxicity and to evaluate effects on quality of life (QOL). RESULTS: 
      Between September 1997 and December 1999, 36 patients (median age, 58 years) were 
      enrolled in this trial. Patients were stratified into 2 groups: a 
      platinum-sensitive group (n = 12 patients) and a platinum-resistant group (n = 24 
      patients). All 36 patients were evaluable for toxicity, and 27 patients were 
      fully assessable for antitumor response after 2 cycles of therapy. All patients 
      had received prior treatments. No objective responses were noted in the 
      platinum-sensitive group. In the platinum-resistant group, 1 patient had some 
      evidence of antitumor activity indicated by a decrease in serum CA 125 and stable 
      disease on imaging studies for 8 months. No changes were noted in overall patient 
      ratings for any of the five QOL domains. CONCLUSIONS: When it was administered as 
      a single agent, aprinocarsen did not have significant clinical activity in 
      patients with advanced ovarian carcinoma. Further study may be warranted in 
      combination with platinum-based regimens.
CI  - Copyright 2003 American Cancer Society.
FAU - Advani, Ranjana
AU  - Advani R
AD  - Oncology Division, Stanford University Medical Center, 269 Campus Drive, 
      Stanford, CA 94305-5151, USA.
FAU - Peethambaram, Prema
AU  - Peethambaram P
FAU - Lum, Bert L
AU  - Lum BL
FAU - Fisher, George A
AU  - Fisher GA
FAU - Hartmann, Lynn
AU  - Hartmann L
FAU - Long, Harry J
AU  - Long HJ
FAU - Halsey, Joanne
AU  - Halsey J
FAU - Holmlund, Jon T
AU  - Holmlund JT
FAU - Dorr, Andrew
AU  - Dorr A
FAU - Sikic, Branimir I
AU  - Sikic BI
LA  - eng
GR  - CA 27469-21/CA/NCI NIH HHS/United States
GR  - M01 RR 00070/RR/NCRR NIH HHS/United States
GR  - R01 CA 52168/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Oligodeoxyribonucleotides, Antisense)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Thionucleotides)
RN  - 151879-73-1 (ISIS 3521)
RN  - EC 2.7.11.13 (PRKCA protein, human)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.13 (Protein Kinase C-alpha)
SB  - IM
MH  - Aged
MH  - Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Infusions, Intravenous
MH  - Middle Aged
MH  - Oligodeoxyribonucleotides, Antisense/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Oligonucleotides, Antisense/administration & dosage/adverse effects/*therapeutic 
      use
MH  - Ovarian Neoplasms/*drug therapy
MH  - Protein Kinase C/*antagonists & inhibitors
MH  - Protein Kinase C-alpha
MH  - Quality of Life
MH  - Self-Assessment
MH  - Thionucleotides/administration & dosage/adverse effects/*therapeutic use
EDAT- 2004/01/13 05:00
MHDA- 2004/01/31 05:00
CRDT- 2004/01/13 05:00
PHST- 2004/01/13 05:00 [pubmed]
PHST- 2004/01/31 05:00 [medline]
PHST- 2004/01/13 05:00 [entrez]
AID - 10.1002/cncr.11909 [doi]
PST - ppublish
SO  - Cancer. 2004 Jan 15;100(2):321-6. doi: 10.1002/cncr.11909.