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

• Published in: Investigational new drugs 2010-02, Vol.28 (1), p.91-97
• Main Authors: Traynor, Anne M., Lee, Ju-Whei, Bayer, Gerald K., Tate, John M., Thomas, Sachdev P., Mazurczak, Miroslaw, Graham, David L., Kolesar, Jill M., Schiller, Joan H.
• Format: Article
• Language: English
• Subjects: Aged; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette Sub-Family B Member 2; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Chemotherapy; Combination therapy; Cooperative Behavior; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Drug dosages; Female; Genotype; Hospitals; Humans; Hypoxia; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Medical Oncology; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Staging; Oncology; Pharmaceuticals; Pharmacology; Pharmacology/Toxicology; Phase II Studies; Polymorphism; Polyvinyl chloride; Public health; Pyridines - adverse effects; Pyridines - therapeutic use; Ribonucleotide reductase; Survival Analysis; Thiosemicarbazones - adverse effects; Thiosemicarbazones - therapeutic use; Time Factors; Toxicity; Treatment Outcome
• ISSN: 0167-6997; 1573-0646
• 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/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.