Phase III study of gemcitabine and cisplatin with or without aprinocarsen, a protein kinase C-alpha antisense oligonucleotide, in patients with advanced-stage non-small-cell lung cancer

Luis Paz-Ares, Jean Yves Douillard, Piotr Koralewski, Christian Manegold, Egbert F. Smit, José Miguel Reyes, Gee Chen Chang, William J. John, Patrick M. Peterson, Coleman K. Obasaju, Michael Lahn, David R Gandara

Research output: Contribution to journalArticle

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Abstract

Purpose: To determine whether aprinocarsen, an antisense oligonucleotide directed against protein kinase C-alpha, when added to the chemotherapy regimen of gemcitabine and cisplatin improved survival in patients with advanced non-small-cell lung cancer (NSCLC). Patients and Methods: Patients with previously untreated stage IIIB/IV NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1, were randomly assigned to either a control arm of gemcitabine 1,250 mg/m2 on days 1 and 8 and cisplatin 80 mg/m 2 on day 1, or experimental arms consisting of the identical chemotherapy plus aprinocarsen 2 mg/kg/d as continuous infusion for 14 days, starting on either day 1 or 3 days before chemotherapy. Cycles were repeated every 21 days. Results: A total of 670 patients were randomly assigned between the control (n = 328) and experimental arms (n = 342). Due to the results from another phase III study of aprinocarsen in NSCLC, further enrollment was stopped, and the study was terminated early. The median number of cycles was four on the control arm and three on the combined experimental arms. Median overall survival was not different between the two groups (control, 10.4 months [95% CI, 8.6 to 12.2]; experimental, 10.0 months [95% CI, 8.4 to 10.8]; P = .613; hazard ratio = 1.05 [95% CI, 0.88 to 1.25]). Response rates (control arm, 35.0%; experimental arms, 28.9%; P = .124) and other time-to-event measures were not significantly different. Grade 3 and 4 toxicities were significantly increased for thrombocytopenia (P< .0001), epistaxis, and thrombosis/embolism in the experimental arms. Conclusion: Adding aprinocarsen to gemcitabine and cisplatin regimen did not enhance survival and other efficacy measures in patients with advanced NSCLC.

Original languageEnglish (US)
Pages (from-to)1428-1434
Number of pages7
JournalJournal of Clinical Oncology
Volume24
Issue number9
DOIs
StatePublished - Mar 20 2006

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gemcitabine
Protein Kinase C-alpha
Antisense Oligonucleotides
Non-Small Cell Lung Carcinoma
Cisplatin
Drug Therapy
Survival
Embolism and Thrombosis
Epistaxis
Thrombocytopenia
aprinocarsen
Control Groups

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Phase III study of gemcitabine and cisplatin with or without aprinocarsen, a protein kinase C-alpha antisense oligonucleotide, in patients with advanced-stage non-small-cell lung cancer. / Paz-Ares, Luis; Douillard, Jean Yves; Koralewski, Piotr; Manegold, Christian; Smit, Egbert F.; Reyes, José Miguel; Chang, Gee Chen; John, William J.; Peterson, Patrick M.; Obasaju, Coleman K.; Lahn, Michael; Gandara, David R.

In: Journal of Clinical Oncology, Vol. 24, No. 9, 20.03.2006, p. 1428-1434.

Research output: Contribution to journalArticle

Paz-Ares, Luis ; Douillard, Jean Yves ; Koralewski, Piotr ; Manegold, Christian ; Smit, Egbert F. ; Reyes, José Miguel ; Chang, Gee Chen ; John, William J. ; Peterson, Patrick M. ; Obasaju, Coleman K. ; Lahn, Michael ; Gandara, David R. / Phase III study of gemcitabine and cisplatin with or without aprinocarsen, a protein kinase C-alpha antisense oligonucleotide, in patients with advanced-stage non-small-cell lung cancer. In: Journal of Clinical Oncology. 2006 ; Vol. 24, No. 9. pp. 1428-1434.
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abstract = "Purpose: To determine whether aprinocarsen, an antisense oligonucleotide directed against protein kinase C-alpha, when added to the chemotherapy regimen of gemcitabine and cisplatin improved survival in patients with advanced non-small-cell lung cancer (NSCLC). Patients and Methods: Patients with previously untreated stage IIIB/IV NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1, were randomly assigned to either a control arm of gemcitabine 1,250 mg/m2 on days 1 and 8 and cisplatin 80 mg/m 2 on day 1, or experimental arms consisting of the identical chemotherapy plus aprinocarsen 2 mg/kg/d as continuous infusion for 14 days, starting on either day 1 or 3 days before chemotherapy. Cycles were repeated every 21 days. Results: A total of 670 patients were randomly assigned between the control (n = 328) and experimental arms (n = 342). Due to the results from another phase III study of aprinocarsen in NSCLC, further enrollment was stopped, and the study was terminated early. The median number of cycles was four on the control arm and three on the combined experimental arms. Median overall survival was not different between the two groups (control, 10.4 months [95{\%} CI, 8.6 to 12.2]; experimental, 10.0 months [95{\%} CI, 8.4 to 10.8]; P = .613; hazard ratio = 1.05 [95{\%} CI, 0.88 to 1.25]). Response rates (control arm, 35.0{\%}; experimental arms, 28.9{\%}; P = .124) and other time-to-event measures were not significantly different. Grade 3 and 4 toxicities were significantly increased for thrombocytopenia (P< .0001), epistaxis, and thrombosis/embolism in the experimental arms. Conclusion: Adding aprinocarsen to gemcitabine and cisplatin regimen did not enhance survival and other efficacy measures in patients with advanced NSCLC.",
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T1 - Phase III study of gemcitabine and cisplatin with or without aprinocarsen, a protein kinase C-alpha antisense oligonucleotide, in patients with advanced-stage non-small-cell lung cancer

AU - Paz-Ares, Luis

AU - Douillard, Jean Yves

AU - Koralewski, Piotr

AU - Manegold, Christian

AU - Smit, Egbert F.

AU - Reyes, José Miguel

AU - Chang, Gee Chen

AU - John, William J.

AU - Peterson, Patrick M.

AU - Obasaju, Coleman K.

AU - Lahn, Michael

AU - Gandara, David R

PY - 2006/3/20

Y1 - 2006/3/20

N2 - Purpose: To determine whether aprinocarsen, an antisense oligonucleotide directed against protein kinase C-alpha, when added to the chemotherapy regimen of gemcitabine and cisplatin improved survival in patients with advanced non-small-cell lung cancer (NSCLC). Patients and Methods: Patients with previously untreated stage IIIB/IV NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1, were randomly assigned to either a control arm of gemcitabine 1,250 mg/m2 on days 1 and 8 and cisplatin 80 mg/m 2 on day 1, or experimental arms consisting of the identical chemotherapy plus aprinocarsen 2 mg/kg/d as continuous infusion for 14 days, starting on either day 1 or 3 days before chemotherapy. Cycles were repeated every 21 days. Results: A total of 670 patients were randomly assigned between the control (n = 328) and experimental arms (n = 342). Due to the results from another phase III study of aprinocarsen in NSCLC, further enrollment was stopped, and the study was terminated early. The median number of cycles was four on the control arm and three on the combined experimental arms. Median overall survival was not different between the two groups (control, 10.4 months [95% CI, 8.6 to 12.2]; experimental, 10.0 months [95% CI, 8.4 to 10.8]; P = .613; hazard ratio = 1.05 [95% CI, 0.88 to 1.25]). Response rates (control arm, 35.0%; experimental arms, 28.9%; P = .124) and other time-to-event measures were not significantly different. Grade 3 and 4 toxicities were significantly increased for thrombocytopenia (P< .0001), epistaxis, and thrombosis/embolism in the experimental arms. Conclusion: Adding aprinocarsen to gemcitabine and cisplatin regimen did not enhance survival and other efficacy measures in patients with advanced NSCLC.

AB - Purpose: To determine whether aprinocarsen, an antisense oligonucleotide directed against protein kinase C-alpha, when added to the chemotherapy regimen of gemcitabine and cisplatin improved survival in patients with advanced non-small-cell lung cancer (NSCLC). Patients and Methods: Patients with previously untreated stage IIIB/IV NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1, were randomly assigned to either a control arm of gemcitabine 1,250 mg/m2 on days 1 and 8 and cisplatin 80 mg/m 2 on day 1, or experimental arms consisting of the identical chemotherapy plus aprinocarsen 2 mg/kg/d as continuous infusion for 14 days, starting on either day 1 or 3 days before chemotherapy. Cycles were repeated every 21 days. Results: A total of 670 patients were randomly assigned between the control (n = 328) and experimental arms (n = 342). Due to the results from another phase III study of aprinocarsen in NSCLC, further enrollment was stopped, and the study was terminated early. The median number of cycles was four on the control arm and three on the combined experimental arms. Median overall survival was not different between the two groups (control, 10.4 months [95% CI, 8.6 to 12.2]; experimental, 10.0 months [95% CI, 8.4 to 10.8]; P = .613; hazard ratio = 1.05 [95% CI, 0.88 to 1.25]). Response rates (control arm, 35.0%; experimental arms, 28.9%; P = .124) and other time-to-event measures were not significantly different. Grade 3 and 4 toxicities were significantly increased for thrombocytopenia (P< .0001), epistaxis, and thrombosis/embolism in the experimental arms. Conclusion: Adding aprinocarsen to gemcitabine and cisplatin regimen did not enhance survival and other efficacy measures in patients with advanced NSCLC.

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