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.

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/m(2) IV on days 1, 8, and 15, and gemcitabine 1,000 mg/m(2) 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.