Randomized phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: National Cancer Institute of Canada-Clinical Trials Group Study BR. 18

Natasha B. Leighl, Luis Paz-Ares, Jean Yves Douillard, Christian Peschel, Andrew Arnold, Alain Depierre, Armando Santoro, Daniel C. Betticher, Ulrich Gatzemeier, Jacek Jassem, Jeffrey Crawford, Dongsheng Tu, Andrea Bezjak, Jeffrey S. Humphrey, Maurizio Voi, Susan Galbraith, Katherine Hann, Lesley Seymour, Frances A. Shepherd

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Abstract

Purpose: To determine whether BMS-275291, a broad-spectrum matrix metalloproteinase inhibitor (MMPI), added to systemic chemotherapy improved survival in advanced non-small-cell lung cancer (NSCLC). In early phase studies, BMS- 275291 was not associated with dose-limiting joint toxicity seen with other MMPIs. Patients and Methods: Chemotherapy-naive patients with stage IIIB/IV NSCLC, performance status (PS) 0 to 2, and adequate organ function were eligible. All patients received paclitaxel 200 mg/m2 plus carboplatin (area under the curve, 6 mg/mL-min) intravenously every 21 days for up to 8 cycles, and were randomly assigned to receive BMS-275291, 1,200 mg orally daily, or placebo until disease progression. The primary study end point was survival (OS); secondary end points included progression-free survival (PFS), response rates (RR), toxicity, and quality of life. Results: From 2000 to 2002, 774 patients were randomly assigned. Pretreatment characteristics were well balanced between arms: median age, 61 years; male sex, 73%; stage IV, 79%; PS 0 to 1, 88%. Interim safety analysis revealed no survival advantage and increased toxicity in the experimental arm, and study treatment was stopped. Median OS, PFS and RR in the final analysis in the BMS-275291 arm were 8.6 months, 4.9 months, and 25.8% respectively, and in the control arm 9.2 months, 5.3 months, 33.7%. Toxicity was significantly higher in the BMS-275291 arm, including flu-like symptoms, rash, hypersensitivity reactions (8.6% v 2.4%), and febrile neutropenia (9.7% v 5.5%). Conclusion: BMS-275291 added to chemotherapy increases toxicity and does not improve survival in advanced NSCLC.

Original languageEnglish
Pages (from-to)2831-2839
Number of pages9
JournalJournal of Clinical Oncology
Volume23
Issue number12
DOIs
Publication statusPublished - Apr 20 2005

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Matrix Metalloproteinase Inhibitors
National Cancer Institute (U.S.)
Carboplatin
Paclitaxel
Non-Small Cell Lung Carcinoma
Canada
Clinical Trials
Survival
Drug Therapy
Disease-Free Survival
Survival Rate
Febrile Neutropenia
MMPI
Exanthema
Area Under Curve
Disease Progression
N-((2S)-2-mercapto-1-oxo-4-(3,4,4- trimethyl-2,5-dioxo-1-imidazolidinyl)butyl)-L-leucyl-N,3- dimethyl-L-Valinamide
Hypersensitivity
Joints
Placebos

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Randomized phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer : National Cancer Institute of Canada-Clinical Trials Group Study BR. 18. / Leighl, Natasha B.; Paz-Ares, Luis; Douillard, Jean Yves; Peschel, Christian; Arnold, Andrew; Depierre, Alain; Santoro, Armando; Betticher, Daniel C.; Gatzemeier, Ulrich; Jassem, Jacek; Crawford, Jeffrey; Tu, Dongsheng; Bezjak, Andrea; Humphrey, Jeffrey S.; Voi, Maurizio; Galbraith, Susan; Hann, Katherine; Seymour, Lesley; Shepherd, Frances A.

In: Journal of Clinical Oncology, Vol. 23, No. 12, 20.04.2005, p. 2831-2839.

Research output: Contribution to journalArticle

Leighl, NB, Paz-Ares, L, Douillard, JY, Peschel, C, Arnold, A, Depierre, A, Santoro, A, Betticher, DC, Gatzemeier, U, Jassem, J, Crawford, J, Tu, D, Bezjak, A, Humphrey, JS, Voi, M, Galbraith, S, Hann, K, Seymour, L & Shepherd, FA 2005, 'Randomized phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: National Cancer Institute of Canada-Clinical Trials Group Study BR. 18', Journal of Clinical Oncology, vol. 23, no. 12, pp. 2831-2839. https://doi.org/10.1200/JCO.2005.04.044
Leighl, Natasha B. ; Paz-Ares, Luis ; Douillard, Jean Yves ; Peschel, Christian ; Arnold, Andrew ; Depierre, Alain ; Santoro, Armando ; Betticher, Daniel C. ; Gatzemeier, Ulrich ; Jassem, Jacek ; Crawford, Jeffrey ; Tu, Dongsheng ; Bezjak, Andrea ; Humphrey, Jeffrey S. ; Voi, Maurizio ; Galbraith, Susan ; Hann, Katherine ; Seymour, Lesley ; Shepherd, Frances A. / Randomized phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer : National Cancer Institute of Canada-Clinical Trials Group Study BR. 18. In: Journal of Clinical Oncology. 2005 ; Vol. 23, No. 12. pp. 2831-2839.
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abstract = "Purpose: To determine whether BMS-275291, a broad-spectrum matrix metalloproteinase inhibitor (MMPI), added to systemic chemotherapy improved survival in advanced non-small-cell lung cancer (NSCLC). In early phase studies, BMS- 275291 was not associated with dose-limiting joint toxicity seen with other MMPIs. Patients and Methods: Chemotherapy-naive patients with stage IIIB/IV NSCLC, performance status (PS) 0 to 2, and adequate organ function were eligible. All patients received paclitaxel 200 mg/m2 plus carboplatin (area under the curve, 6 mg/mL-min) intravenously every 21 days for up to 8 cycles, and were randomly assigned to receive BMS-275291, 1,200 mg orally daily, or placebo until disease progression. The primary study end point was survival (OS); secondary end points included progression-free survival (PFS), response rates (RR), toxicity, and quality of life. Results: From 2000 to 2002, 774 patients were randomly assigned. Pretreatment characteristics were well balanced between arms: median age, 61 years; male sex, 73{\%}; stage IV, 79{\%}; PS 0 to 1, 88{\%}. Interim safety analysis revealed no survival advantage and increased toxicity in the experimental arm, and study treatment was stopped. Median OS, PFS and RR in the final analysis in the BMS-275291 arm were 8.6 months, 4.9 months, and 25.8{\%} respectively, and in the control arm 9.2 months, 5.3 months, 33.7{\%}. Toxicity was significantly higher in the BMS-275291 arm, including flu-like symptoms, rash, hypersensitivity reactions (8.6{\%} v 2.4{\%}), and febrile neutropenia (9.7{\%} v 5.5{\%}). Conclusion: BMS-275291 added to chemotherapy increases toxicity and does not improve survival in advanced NSCLC.",
author = "Leighl, {Natasha B.} and Luis Paz-Ares and Douillard, {Jean Yves} and Christian Peschel and Andrew Arnold and Alain Depierre and Armando Santoro and Betticher, {Daniel C.} and Ulrich Gatzemeier and Jacek Jassem and Jeffrey Crawford and Dongsheng Tu and Andrea Bezjak and Humphrey, {Jeffrey S.} and Maurizio Voi and Susan Galbraith and Katherine Hann and Lesley Seymour and Shepherd, {Frances A.}",
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T1 - Randomized phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer

T2 - National Cancer Institute of Canada-Clinical Trials Group Study BR. 18

AU - Leighl, Natasha B.

AU - Paz-Ares, Luis

AU - Douillard, Jean Yves

AU - Peschel, Christian

AU - Arnold, Andrew

AU - Depierre, Alain

AU - Santoro, Armando

AU - Betticher, Daniel C.

AU - Gatzemeier, Ulrich

AU - Jassem, Jacek

AU - Crawford, Jeffrey

AU - Tu, Dongsheng

AU - Bezjak, Andrea

AU - Humphrey, Jeffrey S.

AU - Voi, Maurizio

AU - Galbraith, Susan

AU - Hann, Katherine

AU - Seymour, Lesley

AU - Shepherd, Frances A.

PY - 2005/4/20

Y1 - 2005/4/20

N2 - Purpose: To determine whether BMS-275291, a broad-spectrum matrix metalloproteinase inhibitor (MMPI), added to systemic chemotherapy improved survival in advanced non-small-cell lung cancer (NSCLC). In early phase studies, BMS- 275291 was not associated with dose-limiting joint toxicity seen with other MMPIs. Patients and Methods: Chemotherapy-naive patients with stage IIIB/IV NSCLC, performance status (PS) 0 to 2, and adequate organ function were eligible. All patients received paclitaxel 200 mg/m2 plus carboplatin (area under the curve, 6 mg/mL-min) intravenously every 21 days for up to 8 cycles, and were randomly assigned to receive BMS-275291, 1,200 mg orally daily, or placebo until disease progression. The primary study end point was survival (OS); secondary end points included progression-free survival (PFS), response rates (RR), toxicity, and quality of life. Results: From 2000 to 2002, 774 patients were randomly assigned. Pretreatment characteristics were well balanced between arms: median age, 61 years; male sex, 73%; stage IV, 79%; PS 0 to 1, 88%. Interim safety analysis revealed no survival advantage and increased toxicity in the experimental arm, and study treatment was stopped. Median OS, PFS and RR in the final analysis in the BMS-275291 arm were 8.6 months, 4.9 months, and 25.8% respectively, and in the control arm 9.2 months, 5.3 months, 33.7%. Toxicity was significantly higher in the BMS-275291 arm, including flu-like symptoms, rash, hypersensitivity reactions (8.6% v 2.4%), and febrile neutropenia (9.7% v 5.5%). Conclusion: BMS-275291 added to chemotherapy increases toxicity and does not improve survival in advanced NSCLC.

AB - Purpose: To determine whether BMS-275291, a broad-spectrum matrix metalloproteinase inhibitor (MMPI), added to systemic chemotherapy improved survival in advanced non-small-cell lung cancer (NSCLC). In early phase studies, BMS- 275291 was not associated with dose-limiting joint toxicity seen with other MMPIs. Patients and Methods: Chemotherapy-naive patients with stage IIIB/IV NSCLC, performance status (PS) 0 to 2, and adequate organ function were eligible. All patients received paclitaxel 200 mg/m2 plus carboplatin (area under the curve, 6 mg/mL-min) intravenously every 21 days for up to 8 cycles, and were randomly assigned to receive BMS-275291, 1,200 mg orally daily, or placebo until disease progression. The primary study end point was survival (OS); secondary end points included progression-free survival (PFS), response rates (RR), toxicity, and quality of life. Results: From 2000 to 2002, 774 patients were randomly assigned. Pretreatment characteristics were well balanced between arms: median age, 61 years; male sex, 73%; stage IV, 79%; PS 0 to 1, 88%. Interim safety analysis revealed no survival advantage and increased toxicity in the experimental arm, and study treatment was stopped. Median OS, PFS and RR in the final analysis in the BMS-275291 arm were 8.6 months, 4.9 months, and 25.8% respectively, and in the control arm 9.2 months, 5.3 months, 33.7%. Toxicity was significantly higher in the BMS-275291 arm, including flu-like symptoms, rash, hypersensitivity reactions (8.6% v 2.4%), and febrile neutropenia (9.7% v 5.5%). Conclusion: BMS-275291 added to chemotherapy increases toxicity and does not improve survival in advanced NSCLC.

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