Literature DB >> 19238328

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.

Anne M Traynor1, Ju-Whei Lee, Gerald K Bayer, John M Tate, Sachdev P Thomas, Miroslaw Mazurczak, David L Graham, Jill M Kolesar, Joan H Schiller.   

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.

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Year:  2009        PMID: 19238328      PMCID: PMC3045859          DOI: 10.1007/s10637-009-9230-z

Source DB:  PubMed          Journal:  Invest New Drugs        ISSN: 0167-6997            Impact factor:   3.850


  26 in total

1.  Increased sensitivity of hydroxyurea-resistant leukemic cells to gemcitabine.

Authors:  S J Wong; M S Myette; J P Wereley; C R Chitambar
Journal:  Clin Cancer Res       Date:  1999-02       Impact factor: 12.531

2.  Suppression of lung tumor formation by the regulatory subunit of ribonucleotide reductase.

Authors:  Ashish Gautam; Gerold Bepler
Journal:  Cancer Res       Date:  2006-07-01       Impact factor: 12.701

Review 3.  Chelators at the cancer coalface: desferrioxamine to Triapine and beyond.

Authors:  Yu Yu; Jacky Wong; David B Lovejoy; Danuta S Kalinowski; Des R Richardson
Journal:  Clin Cancer Res       Date:  2006-12-01       Impact factor: 12.531

4.  RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer.

Authors:  Gerold Bepler; Irina Kusmartseva; Swati Sharma; Ashish Gautam; Alan Cantor; Anupama Sharma; George Simon
Journal:  J Clin Oncol       Date:  2006-09-11       Impact factor: 44.544

Review 5.  Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense.

Authors:  Elaine M Leslie; Roger G Deeley; Susan P C Cole
Journal:  Toxicol Appl Pharmacol       Date:  2005-05-01       Impact factor: 4.219

6.  The synergistic interaction of gemcitabine and cytosine arabinoside with the ribonucleotide reductase inhibitor triapine is schedule dependent.

Authors:  J Sigmond; J A E Kamphuis; A C Laan; E K Hoebe; A M Bergman; G J Peters
Journal:  Biochem Pharmacol       Date:  2007-01-21       Impact factor: 5.858

7.  DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer.

Authors:  Zhong Zheng; Tingan Chen; Xueli Li; Eric Haura; Anupama Sharma; Gerold Bepler
Journal:  N Engl J Med       Date:  2007-02-22       Impact factor: 91.245

8.  A multicenter phase II trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine) and gemcitabine in advanced non-small-cell lung cancer with pharmacokinetic evaluation using peripheral blood mononuclear cells.

Authors:  Brigette Ma; Boon Cher Goh; Eng Huat Tan; Kwok Chi Lam; Ross Soo; Swan Swan Leong; Ling Zhi Wang; Frankie Mo; Anthony T C Chan; Benny Zee; Tony Mok
Journal:  Invest New Drugs       Date:  2007-09-12       Impact factor: 3.850

9.  Pharmacogenomic and pharmacokinetic determinants of erlotinib toxicity.

Authors:  Charles M Rudin; Wanqing Liu; Apurva Desai; Theodore Karrison; Xuemin Jiang; Linda Janisch; Soma Das; Jacqueline Ramirez; Balasubramanian Poonkuzhali; Erin Schuetz; Donna Lee Fackenthal; Peixian Chen; Deborah K Armstrong; Julie R Brahmer; Gini F Fleming; Everett E Vokes; Michael A Carducci; Mark J Ratain
Journal:  J Clin Oncol       Date:  2008-03-01       Impact factor: 44.544

10.  Ribonucleotide reductase subunits M1 and M2 mRNA expression levels and clinical outcome of lung adenocarcinoma patients treated with docetaxel/gemcitabine.

Authors:  J Souglakos; I Boukovinas; M Taron; P Mendez; D Mavroudis; M Tripaki; D Hatzidaki; A Koutsopoulos; E Stathopoulos; V Georgoulias; R Rosell
Journal:  Br J Cancer       Date:  2008-04-15       Impact factor: 7.640

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  27 in total

1.  Population pharmacokinetics of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (Triapine®) in cancer patients.

Authors:  Jill Kolesar; Richard C Brundage; Marcia Pomplun; Dona Alberti; Kyle Holen; Anne Traynor; Percy Ivy; George Wilding
Journal:  Cancer Chemother Pharmacol       Date:  2010-05-04       Impact factor: 3.333

Review 2.  Iron and Cancer.

Authors:  Suzy V Torti; David H Manz; Bibbin T Paul; Nicole Blanchette-Farra; Frank M Torti
Journal:  Annu Rev Nutr       Date:  2018-08-21       Impact factor: 11.848

3.  A phase I and pharmacokinetic study of oral 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) in the treatment of advanced-stage solid cancers: a California Cancer Consortium Study.

Authors:  Joseph Chao; Timothy W Synold; Robert J Morgan; Charles Kunos; Jeff Longmate; Heinz-Josef Lenz; Dean Lim; Stephen Shibata; Vincent Chung; Ronald G Stoller; Chandra P Belani; David R Gandara; Mark McNamara; Barbara J Gitlitz; Derick H Lau; Suresh S Ramalingam; Angela Davies; Igor Espinoza-Delgado; Edward M Newman; Yun Yen
Journal:  Cancer Chemother Pharmacol       Date:  2011-11-22       Impact factor: 3.333

4.  Cytotoxic Evaluation of 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone, 3-AP, in Peripheral Blood Lymphocytes of Patients with Refractory Solid Tumors using Electron Paramagnetic Resonance.

Authors:  Jill M Kolesar; Kamakshi Sachidanandam; William R Schelman; Jens Eickhoff; Kyle D Holen; Anne M Traynor; Dona B Alberti; James P Thomas; Christopher R Chitambar; George Wilding; William E Antholine
Journal:  Exp Ther Med       Date:  2011-01       Impact factor: 2.447

5.  Kinetic studies on the oxidation of oxyhemoglobin by biologically active iron thiosemicarbazone complexes: relevance to iron-chelator-induced methemoglobinemia.

Authors:  Maram T Basha; Carlos Rodríguez; Des R Richardson; Manuel Martínez; Paul V Bernhardt
Journal:  J Biol Inorg Chem       Date:  2013-12-08       Impact factor: 3.358

6.  A phase I study of prolonged infusion of triapine in combination with fixed dose rate gemcitabine in patients with advanced solid tumors.

Authors:  Amir Mortazavi; Yonghua Ling; Ludmila Katherine Martin; Lai Wei; Mitch A Phelps; Zhongfa Liu; Erica J Harper; S Percy Ivy; Xin Wu; Bing-Sen Zhou; Xiyong Liu; Deidre Deam; J Paul Monk; William J Hicks; Yun Yen; Gregory A Otterson; Michael R Grever; Tanios Bekaii-Saab
Journal:  Invest New Drugs       Date:  2012-07-31       Impact factor: 3.850

7.  Cytotoxic activities of new iron(III) and nickel(II) chelates of some S-methyl-thiosemicarbazones on K562 and ECV304 cells.

Authors:  Belkis Atasever; Bahri Ulküseven; Tülay Bal-Demirci; Serap Erdem-Kuruca; Zeynep Solakoğlu
Journal:  Invest New Drugs       Date:  2009-06-04       Impact factor: 3.850

8.  In vitro evaluation of the metabolic enzymes and drug interaction potential of triapine.

Authors:  Anand Joshi; Brian F Kiesel; Nupur Chaphekar; Reyna Jones; Jianxia Guo; Charles A Kunos; Sarah Taylor; Edward Chu; Raman Venkataramanan; Jan H Beumer
Journal:  Cancer Chemother Pharmacol       Date:  2020-09-28       Impact factor: 3.333

9.  Mechanistic studies of semicarbazone triapine targeting human ribonucleotide reductase in vitro and in mammalian cells: tyrosyl radical quenching not involving reactive oxygen species.

Authors:  Yimon Aye; Marcus J C Long; JoAnne Stubbe
Journal:  J Biol Chem       Date:  2012-08-22       Impact factor: 5.157

10.  A ribonucleotide reductase inhibitor with deoxyribonucleoside-reversible cytotoxicity.

Authors:  Mikael Crona; Paula Codó; Venkateswara Rao Jonna; Anders Hofer; Aristi P Fernandes; Fredrik Tholander
Journal:  Mol Oncol       Date:  2016-07-26       Impact factor: 6.603

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