Phase II study of PKC-α antisense oligonucleotide aprinocarsen in combination with gemcitabine and carboplatin in patients with advanced non-small cell lung cancer

Paul Ritch, Charles M. Rudin, Jacob David Bitran, Martin J. Edelman, Alex Makalinao, David Irwin, Rogerio Lilenbaum, Patrick Peterson, William J. John

Research output: Contribution to journalArticle

Abstract

The antisense oligonucleotide aprinocarsen specifically inhibits the transcription of protein kinase C-α. This study evaluated the response rate of the combination therapy of aprinocarsen, gemcitabine, and carboplatin in previously untreated patients with advanced non-small cell lung cancer (NSCLC). Secondary objectives included the measurement of time-to-event efficacy parameters and toxicity. Patients with stage IV or stage IIIB disease (N3 and/or pleural/pericardial effusion) were treated with gemcitabine 1250 mg/m2 on days 1 and 8 and carboplatin AUC 5 on day 1 every 21 days. Aprinocarsen was administered as 2 mg/kg/day continuous iv infusion on the first 14 days of each cycle, following the carboplatin treatment. A total of 36 patients received a median of 3 treatment cycles, with 10 patients completing 6 cycles. No complete response was observed, while partial response was seen in 25% of patients. Stable disease and progressive disease was observed in 36.1% and 22.2% of patients. The median overall survival was 8.3 months, and the median duration of progression-free survival was 5.7 months (95% CI, 3.2-7.1 months). Thrombocytopenia (78%) and neutropenia (50%) were the major grade 3/4 toxicities. Enrollment for this study was stopped and the study was terminated in March 2003 due to the results of a large phase III study, which suggested that aprinocarsen did not improve response or add survival benefit to chemotherapy in advanced NSCLC. The addition of aprinocarsen to gemcitabine + carboplatin therapy in patients with NSCLC showed moderate activity. However, this combination resulted in severe thrombocytopenia in the majority of patients.

Original languageEnglish (US)
Pages (from-to)173-180
Number of pages8
JournalLung Cancer
Volume52
Issue number2
DOIs
StatePublished - May 2006
Externally publishedYes

Fingerprint

gemcitabine
Antisense Oligonucleotides
Carboplatin
Non-Small Cell Lung Carcinoma
Thrombocytopenia
Survival
Pericardial Effusion
aprinocarsen
Pleural Effusion
Therapeutics
Neutropenia
Protein Kinase C
Disease-Free Survival
Area Under Curve

Keywords

  • Advanced non-small cell lung cancer
  • Affinitak
  • Antisense oligonucleotide
  • Aprinocarsen
  • Carboplatin
  • Combination therapy
  • Gemcitabine
  • ISIS
  • LY900003
  • Phase II

ASJC Scopus subject areas

  • Oncology

Cite this

Phase II study of PKC-α antisense oligonucleotide aprinocarsen in combination with gemcitabine and carboplatin in patients with advanced non-small cell lung cancer. / Ritch, Paul; Rudin, Charles M.; Bitran, Jacob David; Edelman, Martin J.; Makalinao, Alex; Irwin, David; Lilenbaum, Rogerio; Peterson, Patrick; John, William J.

In: Lung Cancer, Vol. 52, No. 2, 05.2006, p. 173-180.

Research output: Contribution to journalArticle

Ritch, P, Rudin, CM, Bitran, JD, Edelman, MJ, Makalinao, A, Irwin, D, Lilenbaum, R, Peterson, P & John, WJ 2006, 'Phase II study of PKC-α antisense oligonucleotide aprinocarsen in combination with gemcitabine and carboplatin in patients with advanced non-small cell lung cancer', Lung Cancer, vol. 52, no. 2, pp. 173-180. https://doi.org/10.1016/j.lungcan.2005.12.012
Ritch, Paul ; Rudin, Charles M. ; Bitran, Jacob David ; Edelman, Martin J. ; Makalinao, Alex ; Irwin, David ; Lilenbaum, Rogerio ; Peterson, Patrick ; John, William J. / Phase II study of PKC-α antisense oligonucleotide aprinocarsen in combination with gemcitabine and carboplatin in patients with advanced non-small cell lung cancer. In: Lung Cancer. 2006 ; Vol. 52, No. 2. pp. 173-180.
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abstract = "The antisense oligonucleotide aprinocarsen specifically inhibits the transcription of protein kinase C-α. This study evaluated the response rate of the combination therapy of aprinocarsen, gemcitabine, and carboplatin in previously untreated patients with advanced non-small cell lung cancer (NSCLC). Secondary objectives included the measurement of time-to-event efficacy parameters and toxicity. Patients with stage IV or stage IIIB disease (N3 and/or pleural/pericardial effusion) were treated with gemcitabine 1250 mg/m2 on days 1 and 8 and carboplatin AUC 5 on day 1 every 21 days. Aprinocarsen was administered as 2 mg/kg/day continuous iv infusion on the first 14 days of each cycle, following the carboplatin treatment. A total of 36 patients received a median of 3 treatment cycles, with 10 patients completing 6 cycles. No complete response was observed, while partial response was seen in 25{\%} of patients. Stable disease and progressive disease was observed in 36.1{\%} and 22.2{\%} of patients. The median overall survival was 8.3 months, and the median duration of progression-free survival was 5.7 months (95{\%} CI, 3.2-7.1 months). Thrombocytopenia (78{\%}) and neutropenia (50{\%}) were the major grade 3/4 toxicities. Enrollment for this study was stopped and the study was terminated in March 2003 due to the results of a large phase III study, which suggested that aprinocarsen did not improve response or add survival benefit to chemotherapy in advanced NSCLC. The addition of aprinocarsen to gemcitabine + carboplatin therapy in patients with NSCLC showed moderate activity. However, this combination resulted in severe thrombocytopenia in the majority of patients.",
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