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).


CONCLUSIONS
This regimen did not demonstrate activity in relapsed NSCLC. Prolonged survival seen with MDR1 variant genotypes is hypothesis-generating.
Traynor
Anne M
AM
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin School of Medicine and Public Health, K6/568 CSC, #5669, 600 Highland Avenue, Madison, WI, 53792, USA. amt@medicine.wisc.edu
Lee
Ju-Whei
JW
Bayer
Gerald K
GK
Tate
John M
JM
Thomas
Sachdev P
SP
Mazurczak
Miroslaw
M
Graham
David L
DL
Kolesar
Jill M
JM
Schiller
Joan H
JH
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003299:Cooperative Behavior; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008495:Medical Oncology; D008875:Middle Aged; D009367:Neoplasm Staging; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use; D016019:Survival Analysis; D013882:Thiosemicarbazones / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D000093542:Gemcitabine
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D011725:Pyridines; C073119:TAP1 protein, human; D013882:Thiosemicarbazones; D003841:Deoxycytidine; C078157:3-aminopyridine-2-carboxaldehyde thiosemicarbazone; D000093542:Gemcitabine