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

Invest New Drugs. 2010 Feb;28(1):91-7. doi: 10.1007/s10637-009-9230-z. Epub 2009 Feb 24.

Abstract

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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cooperative Behavior*
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Female
  • Gemcitabine
  • Genotype
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Medical Oncology*
  • Middle Aged
  • Neoplasm Staging
  • Pyridines / adverse effects
  • Pyridines / therapeutic use
  • Survival Analysis
  • Thiosemicarbazones / adverse effects
  • Thiosemicarbazones / therapeutic use
  • Time Factors
  • Treatment Outcome

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • Pyridines
  • TAP1 protein, human
  • Thiosemicarbazones
  • Deoxycytidine
  • 3-aminopyridine-2-carboxaldehyde thiosemicarbazone
  • Gemcitabine

Grants and funding