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. Traynor; Ju Whei Lee; Gerald K. Bayer; John M. Tate; Sachdev P. Thomas; Miroslaw Mazurczak; David L. Graham; Jill M. Kolesar; Joan H. Schiller

doi:10.1007/s10637-009-9230-z

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

Producción científica: Article › revisión exhaustiva

108 Citas (Scopus)

Resumen

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/m² IV on days 1, 8, and 15, and gemcitabine 1,000 mg/m² 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.

Idioma original	English
Páginas (desde-hasta)	91-97
Número de páginas	7
Publicación	Investigational New Drugs
Volumen	28
N.º	1
DOI	https://doi.org/10.1007/s10637-009-9230-z
Estado	Published - ene 2010

Nota bibliográfica

Funding Information:
Acknowledgments The authors thank the patients who participated in this trial, as well as the investigators who enrolled patients, and the data managers, and the clinical and research nurses who brought this trial to completion. This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M.D., Chair) and supported in part by the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center K12 CA087716 and 5 P30 CA014520-35, and by the Public Health Service Grants CA23318, CA66636, CA21115, CA21076, and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.

Funding Information:
This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M.D., Chair) and supported in part by the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center K12 CA087716 and 5 P30 CA014520-35, and by the Public Health Service Grants CA23318, CA66636, CA21115, CA21076, and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. A.M.Traynor(*) . J. M. Kolesar 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 e-mail: [email protected]

Financiación

Acknowledgments The authors thank the patients who participated in this trial, as well as the investigators who enrolled patients, and the data managers, and the clinical and research nurses who brought this trial to completion. This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M.D., Chair) and supported in part by the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center K12 CA087716 and 5 P30 CA014520-35, and by the Public Health Service Grants CA23318, CA66636, CA21115, CA21076, and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M.D., Chair) and supported in part by the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center K12 CA087716 and 5 P30 CA014520-35, and by the Public Health Service Grants CA23318, CA66636, CA21115, CA21076, and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. A.M.Traynor(*) . J. M. Kolesar 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 e-mail: [email protected]

Financiadores	Número del financiador
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	5 P30 CA014520-35, K12 CA087716
National Institutes of Health (NIH)
U.S. Department of Health and Human Services
National Childhood Cancer Registry – National Cancer Institute	U10CA021076
U.S. Public Health Service	CA66636, CA21115, CA23318

ASJC Scopus subject areas

Oncology
Pharmacology
Pharmacology (medical)

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Traynor, A. M., Lee, J. W., Bayer, G. K., Tate, J. M., Thomas, S. P., Mazurczak, M., Graham, D. L., Kolesar, J. M., & Schiller, J. H. (2010). 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. Investigational New Drugs, 28(1), 91-97. https://doi.org/10.1007/s10637-009-9230-z

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title = "A phase II trial of Triapine{\textregistered} (NSC\# 663249) and gemcitabine as second line treatment of advanced non-small cell lung cancer: Eastern Cooperative Oncology Group Study 1503",

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/m2 IV on days 1, 8, and 15, and gemcitabine 1,000 mg/m2 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{\textregistered} 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.",

keywords = "ATP binding cassette transporter, Combination chemotherapy, Non-small cell lung cancer, Ribonucleotide reductase, Single nucleotide polymorphism",

author = "Traynor, \{Anne M.\} and Lee, \{Ju Whei\} and Bayer, \{Gerald K.\} and Tate, \{John M.\} and Thomas, \{Sachdev P.\} and Miroslaw Mazurczak and Graham, \{David L.\} and Kolesar, \{Jill M.\} and Schiller, \{Joan H.\}",

note = "Funding Information: Acknowledgments The authors thank the patients who participated in this trial, as well as the investigators who enrolled patients, and the data managers, and the clinical and research nurses who brought this trial to completion. This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M.D., Chair) and supported in part by the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center K12 CA087716 and 5 P30 CA014520-35, and by the Public Health Service Grants CA23318, CA66636, CA21115, CA21076, and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Funding Information: This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M.D., Chair) and supported in part by the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center K12 CA087716 and 5 P30 CA014520-35, and by the Public Health Service Grants CA23318, CA66636, CA21115, CA21076, and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. A.M.Traynor(*) . J. M. Kolesar 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 e-mail: [email protected]",

year = "2010",

month = jan,

doi = "10.1007/s10637-009-9230-z",

language = "English",

volume = "28",

pages = "91--97",

number = "1",

}

Traynor, AM, Lee, JW, Bayer, GK, Tate, JM, Thomas, SP, Mazurczak, M, Graham, DL, Kolesar, JM & Schiller, JH 2010, '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', Investigational New Drugs, vol. 28, n.º 1, pp. 91-97. https://doi.org/10.1007/s10637-009-9230-z

TY - JOUR

T1 - A phase II trial of Triapine® (NSC# 663249) and gemcitabine as second line treatment of advanced non-small cell lung cancer

T2 - Eastern Cooperative Oncology Group Study 1503

AU - Traynor, Anne M.

AU - Lee, Ju Whei

AU - Bayer, Gerald K.

AU - Tate, John M.

AU - Thomas, Sachdev P.

AU - Mazurczak, Miroslaw

AU - Graham, David L.

AU - Kolesar, Jill M.

AU - Schiller, Joan H.

N1 - Funding Information: Acknowledgments The authors thank the patients who participated in this trial, as well as the investigators who enrolled patients, and the data managers, and the clinical and research nurses who brought this trial to completion. This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M.D., Chair) and supported in part by the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center K12 CA087716 and 5 P30 CA014520-35, and by the Public Health Service Grants CA23318, CA66636, CA21115, CA21076, and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Funding Information: This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M.D., Chair) and supported in part by the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center K12 CA087716 and 5 P30 CA014520-35, and by the Public Health Service Grants CA23318, CA66636, CA21115, CA21076, and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. A.M.Traynor(*) . J. M. Kolesar 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 e-mail: [email protected]

PY - 2010/1

Y1 - 2010/1

N2 - 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/m2 IV on days 1, 8, and 15, and gemcitabine 1,000 mg/m2 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.

AB - 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/m2 IV on days 1, 8, and 15, and gemcitabine 1,000 mg/m2 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.

KW - ATP binding cassette transporter

KW - Combination chemotherapy

KW - Non-small cell lung cancer

KW - Ribonucleotide reductase

KW - Single nucleotide polymorphism

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U2 - 10.1007/s10637-009-9230-z

DO - 10.1007/s10637-009-9230-z

M3 - Article

C2 - 19238328

AN - SCOPUS:74149093251

SN - 0167-6997

VL - 28

SP - 91

EP - 97

JO - Investigational New Drugs

JF - Investigational New Drugs

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ER -

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

Resumen

Nota bibliográfica

Financiación

ASJC Scopus subject areas

ODS de las Naciones Unidas

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