ECOG 1503: A phase II trial of triapine (NSC#663249) with gemcitabine (T/G) as 2 nd line treatment of non-small cell lung cancer (NSCLC)

A. M. Traynor; D. E. Levy; G. K. Bayer; J. M. Tate; S. P. Thomas; M. A. Mazurczak; D. L. Graham; J. M. Kolesar; J. H. Schiller

doi:10.1200/jco.2006.24.18_suppl.17151

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ECOG 1503: A phase II trial of triapine (NSC#663249) with gemcitabine (T/G) as 2 nd line treatment of non-small cell lung cancer (NSCLC)

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ECOG 1503: A phase II trial of triapine (NSC#663249) with gemcitabine (T/G) as 2 nd line treatment of non-small cell lung cancer (NSCLC)

A. M. Traynor, D. E. Levy, G. K. Bayer, J. M. Tate, S. P. Thomas, M. A. Mazurczak, D. L. Graham, J. M. Kolesar and J. H. Schiller

Journal of clinical oncology, Vol.24(18_suppl), pp.17151-17151

06/20/2006

DOI: 10.1200/jco.2006.24.18_suppl.17151

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Abstract

Abstract only 17151 Background: Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone) is a novel chelator of the ribonucleotide reductase (RR) subunit M2. Triapine was shown to enhance cellular uptake and DNA incorporation of gemcitabine in tumor cell lines. Preclinical evidence suggested that cells with the wild-type (wT) MDR1 gene may have lower intratumoral concentrations of Triapine. Objectives: Primary objective was response rate (RR). Secondary objectives included rate of stable disease (SD), progression free survival (PFS), overall survival (OS), and safety of T/G in the 2 nd line treatment of advanced NSCLC. Correlative objectives were to examine the effects of MDR1 polymorphisms, RRM1, RRM2, and p53R2 protein and gene expression, and germline and tumor mutations of p53 on clinical outcomes. Methods: Pts with relapsed NSCLC who failed one prior cytotoxic regimen were eligible; prior gemcitabine was excluded. Treatment: Triapine 105 mg/m 2 IV on days 1, 8, and 15 and gemcitabine 1000 mg/m 2 on days 1, 8, and 15, of a 28 day cycle. Results: 18 pts enrolled from 11/04–1/05. Stage: IIIB (1 pt); IV (17 pts). PS: 0 (4 pts); 1 (14 pts). Median number of cycles administered: 2. No objective antitumor responses were seen. 5 pts experienced SD (range 7–135 days). Median OS: 5.4 mo (95%CI 3.98, not yet reached); median PFS: 3.2 mo (95%CI 1.7, 6.4); estimated 1 yr OS: 39% (SE 13%). Worst Gr 3/4 toxicities: leucopenia (Gr 3–8 pts; Gr 4–1 pt), neutropenia (Gr 3–8 pts; Gr 4–2 pts), hypoxia (Gr 3–4 pts), vomiting (Gr 3–2 pts). Genotyping for MDR1 polymorphisms C1236T, G2677T, and C3435T was performed on all pts. None of the 5 pts with SD were wTs. Pts with wT MDR1 had increased GI and pulmonary toxicity. Additional correlative data will be available for the meeting. Conclusions: T/G did not demonstrate clinically relevant activity in relapsed NSCLC. Genotyping for MDR1 polymorphisms may predict both efficacy and toxicity. [Table: see text]

Details

Title: Subtitle: ECOG 1503: A phase II trial of triapine (NSC#663249) with gemcitabine (T/G) as 2 nd line treatment of non-small cell lung cancer (NSCLC)
Creators: A. M. Traynor - Dana-Farber Cancer Institute
D. E. Levy - Dana-Farber Cancer Institute
G. K. Bayer - Dana-Farber Cancer Institute
J. M. Tate - Dana-Farber Cancer Institute
S. P. Thomas - Dana-Farber Cancer Institute
M. A. Mazurczak - Dana-Farber Cancer Institute
D. L. Graham - Dana-Farber Cancer Institute
J. M. Kolesar - Dana-Farber Cancer Institute
J. H. Schiller - Dana-Farber Cancer Institute
Resource Type: Abstract
Publication Details: Journal of clinical oncology, Vol.24(18_suppl), pp.17151-17151
DOI: 10.1200/jco.2006.24.18_suppl.17151
ISSN: 0732-183X
eISSN: 1527-7755
Language: English
Date published: 06/20/2006
Academic Unit: Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984695800302771

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