title: 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.
abstract: 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.
authors.affiliation: Oncology Division, Stanford University Medical Center, 269 Campus Drive, Stanford, CA 94305-5151, USA.
authors.forename: Ranjana
authors.initials: R
authors.lastname: Advani
authors.forename: Prema
authors.initials: P
authors.lastname: Peethambaram
authors.forename: Bert L
authors.initials: BL
authors.lastname: Lum
authors.forename: George A
authors.initials: GA
authors.lastname: Fisher
authors.forename: Lynn
authors.initials: L
authors.lastname: Hartmann
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Long
authors.forename: Joanne
authors.initials: J
authors.lastname: Halsey
authors.forename: Jon T
authors.initials: JT
authors.lastname: Holmlund
authors.forename: Andrew
authors.initials: A
authors.lastname: Dorr
authors.forename: Branimir I
authors.initials: BI
authors.lastname: Sikic
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051571:Protein Kinase C-alpha; D011788:Quality of Life; D012647:Self-Assessment; D013873:Thionucleotides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D020319:Oligodeoxyribonucleotides, Antisense; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; C108494:ISIS 3521; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha