Investigational New Drugs

, Volume 28, Issue 1, pp 91–97

A phase II trial of Triapine® (NSC# 663249) and gemcitabine as second line treatment of advanced non-small cell lung cancer: Eastern Cooperative Oncology Group Study 1503

  • Anne M. Traynor
  • Ju-Whei Lee
  • Gerald K. Bayer
  • John M. Tate
  • Sachdev P. Thomas
  • Miroslaw Mazurczak
  • David L. Graham
  • Jill M. Kolesar
  • Joan H. Schiller
PHASE II STUDIES

DOI: 10.1007/s10637-009-9230-z

Cite this article as:
Traynor, A.M., Lee, J., Bayer, G.K. et al. Invest New Drugs (2010) 28: 91. doi:10.1007/s10637-009-9230-z

Summary

Background: The objective of ECOG 1503 was to determine the response rate of this combination in the second-line treatment of advanced NSCLC. Methods: Triapine 105 mg/m2 IV on days 1, 8, and 15, and gemcitabine 1,000 mg/m2 on days 1, 8, and 15, of a 28 day cycle. Results: Eighteen patients enrolled. Three patients were not eligible due to protocol violations. No objective antitumor responses were seen. Three patients (20%) experienced stable disease (90% CI 5.7–44%). Median overall survival: 5.4 months (95% CI 4.2–11.6 months); median time to progression: 1.8 months (95% CI 1.7–3.5 months). Five patients developed acute infusion reactions to Triapine® related to elevated methemoglobinemia. Patients with MDR1 variant genotypes of C3435T experienced superior overall survival compared to non-variants (13.3 vs. 4.3 months, respectively, p = 0.023). Conclusion: This regimen did not demonstrate activity in relapsed NSCLC. Prolonged survival seen with MDR1 variant genotypes is hypothesis-generating.

Keywords

Non-small cell lung cancerCombination chemotherapyRibonucleotide reductaseSingle nucleotide polymorphismATP binding cassette transporter

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Anne M. Traynor
    • 1
  • Ju-Whei Lee
    • 2
  • Gerald K. Bayer
    • 3
  • John M. Tate
    • 4
  • Sachdev P. Thomas
    • 5
  • Miroslaw Mazurczak
    • 6
  • David L. Graham
    • 7
  • Jill M. Kolesar
    • 1
  • Joan H. Schiller
    • 8
  1. 1.University of Wisconsin Paul P. Carbone Comprehensive Cancer CenterUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA
  2. 2.Eastern Cooperative Oncology Group and the Department of Biostatistics and Computational BiologyDana-Farber Cancer InstituteBostonUSA
  3. 3.Green Bay Oncology, Saint Vincent HospitalGreen BayUSA
  4. 4.Roger Maris Cancer Center, Merit Care Hospital CCOPFargoUSA
  5. 5.Illinois Cancer CarePeoriaUSA
  6. 6.Sanford Clinic OncologySanford HospitalSioux FallsUSA
  7. 7.Carle Cancer AssociationUrbanaUSA
  8. 8.Division of Hematology and Oncology, Department of Internal MedicineUniversity of Texas at Southwestern Medical CenterDallasUSA