Randomized phase II evaluation of aprinocarsen in combination with gemcitabine and cisplatin for patients with advanced/metastatic non-small cell lung cancer.

Abstract

Aprinocarsen is a specific antisense oligonucleotide inhibitor of protein kinase C-alpha. This study aimed to evaluate the response rate to combination therapy with aprinocarsen, gemcitabine and cisplatin, in chemonaive patients with advanced/metastatic NSCLC. Secondary objectives included comparison of response rate, time to event efficacy parameters, and toxicities on the 2 treatment arms. Patients with stage IV, or stage IIIB disease (N3 and/or pleural/pericardial effusion), were randomized to either control or experimental arm. Patients on both arms received gemcitabine 1250 mg/m2 on days 1 and 8, and cisplatin 80 mg/m2 on day 1 of a 3-week cycle. Additionally, on the experimental arm, aprinocarsen was administered as 2 mg/kg continuous iv infusion on days 1-14, every 21 days. A total of 18 enrolled patients were randomized on the 2 arms. Further enrollment was terminated in March 2003 as a result of a phase III trial suggesting that aprinocarsen did not have an added survival benefit when combined with paclitaxel and carboplatin therapy in patients with NSCLC. Patients received a median of 4 cycles on control arm and 2.5 cycles on experimental arm. The response rate was 16.7% in the experimental arm and 44.4% in the control arm. Most frequent grade 3/4 toxicities were hematologic, with a higher incidence of thrombocytopenia in the experimental arm (87.5% vs. 33.3%). Despite the 14-day continuous infusion schedule, infection rate was not increased in the experimental arm. The present study did not show any advantage, in response rate or secondary endpoints, with aprinocarsen; however, the toxicity was not unduly increased, and aprinocarsen regimen was safely administered.

• Authors: Johan Vansteenkiste, Jean-Luc Canon, Henrik Riska, Robert Pirker, Patrick Peterson, William John, Pekka Mali, Michael Lahn
• Journal: Investigational new drugs (Invest New Drugs) Vol. 23 Issue 3 Pg. 263-9 (Jun 2005) ISSN: 0167-6997 [Print] United States
• PMID: 15868384 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Oligonucleotides, Antisense
• Phosphorothioate Oligonucleotides
• Deoxycytidine
• aprinocarsen
• Cisplatin
• Gemcitabine

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, secondary)
• Cisplatin (administration & dosage)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Female
• Humans
• Lung Neoplasms (drug therapy, pathology)
• Male
• Middle Aged
• Oligonucleotides, Antisense (administration & dosage)
• Phosphorothioate Oligonucleotides
• Gemcitabine