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Investigational New Drugs

, Volume 23, Issue 3, pp 263–269 | Cite as

Randomized phase II evaluation of aprinocarsen in combination with gemcitabine and cisplatin for patients with advanced/metastatic non-small cell lung cancer

  • Johan Vansteenkiste
  • Jean-Luc Canon
  • Henrik Riska
  • Robert Pirker
  • Patrick Peterson
  • William John
  • Pekka Mali
  • Michael LahnEmail author
Article

Summary

Aprinocarsen is a specific antisense oligonucleotide inhibitor of protein kinase C-α. This study aimed to evaluate the response rate to combination therapy with aprinocarsen, gemcitabine and cisplatin, in chemonaive patients with advanced/metastatic NSCLC. Secondary objectives included comparison of response rate, time to event efficacy parameters, and toxicities on the 2 treatment arms. Patients with stage IV, or stage IIIB disease (N3 and/or pleural/pericardial effusion), were randomized to either control or experimental arm. Patients on both arms received gemcitabine 1250 mg/m2 on days 1 and 8, and cisplatin 80 mg/m2 on day 1 of a 3-week cycle. Additionally, on the experimental arm, aprinocarsen was administered as 2 mg/kg continuous iv infusion on days 1–14, every 21 days. A total of 18 enrolled patients were randomized on the 2 arms. Further enrollment was terminated in March 2003 as a result of a phase III trial suggesting that aprinocarsen did not have an added survival benefit when combined with paclitaxel and carboplatin therapy in patients with NSCLC. Patients received a median of 4 cycles on control arm and 2.5 cycles on experimental arm. The response rate was 16.7% in the experimental arm and 44.4% in the control arm. Most frequent grade 3/4 toxicities were hematologic, with a higher incidence of thrombocytopenia in the experimental arm (87.5% vs. 33.3%). Despite the 14-day continuous infusion schedule, infection rate was not increased in the experimental arm. The present study did not show any advantage, in response rate or secondary endpoints, with aprinocarsen; however, the toxicity was not unduly increased, and aprinocarsen regimen was safely administered.

Key words

aprinocarsen cisplatin gemcitabine non-small cell lung cancer phase II 

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Johan Vansteenkiste
    • 1
  • Jean-Luc Canon
    • 2
  • Henrik Riska
    • 3
  • Robert Pirker
    • 4
  • Patrick Peterson
    • 5
  • William John
    • 5
  • Pekka Mali
    • 6
  • Michael Lahn
    • 5
    • 7
    Email author
  1. 1.Universitair Ziekenhuis GasthuisbergLeuvenBelgium
  2. 2.CH Notre Dame et Reine FabiolaCharleroiBelgium
  3. 3.Helsinki University HospitalHelsinkiFinland
  4. 4.AKH WienWienAustria
  5. 5.Eli Lilly and CompanyIndianapolisUSA
  6. 6.Turku University HospitalTurkuFinland
  7. 7.Oncology Therapeutic Area, Lilly Research LaboratoriesLilly Corporate CenterIndianapolisUSA

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