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

Abstract

The antisense oligonucleotide aprinocarsen specifically inhibits the transcription of protein kinase C-alpha. 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 (N(3) and/or pleural/pericardial effusion) were treated with gemcitabine 1,250 mg/m(2) on days 1 and 8 and carboplatin AUC 5 on day 1 every 21 days. Aprinocarsen was administered as 2mg/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.

• Authors: Paul Ritch, Charles M Rudin, Jacob David Bitran, Martin J Edelman, Alex Makalinao, David Irwin, Rogerio Lilenbaum, Patrick Peterson, William J John
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 52 Issue 2 Pg. 173-80 (May 2006) ISSN: 0169-5002 [Print] Ireland
• PMID: 16507327 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Immunosuppressive Agents
• Oligonucleotides, Antisense
• Phosphorothioate Oligonucleotides
• Deoxycytidine
• Carboplatin
• Ribonucleotide Reductases
• Protein Kinase C
• aprinocarsen
• Gemcitabine

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Carboplatin (administration & dosage, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Deoxycytidine (administration & dosage, analogs & derivatives, therapeutic use)
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Humans
• Immunosuppressive Agents (administration & dosage, therapeutic use)
• Lung Neoplasms (drug therapy, pathology)
• Male
• Middle Aged
• Neoplasm Staging
• Oligonucleotides, Antisense (administration & dosage, antagonists & inhibitors, therapeutic use)
• Phosphorothioate Oligonucleotides
• Protein Kinase C (antagonists & inhibitors)
• Retrospective Studies
• Ribonucleotide Reductases (antagonists & inhibitors)
• Treatment Outcome
• Gemcitabine