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

• Published in: Journal of clinical oncology Vol. 24; no. 9; pp. 1428 - 1434
• Main Authors: PAZ-ARES, Luis, DOUILLARD, Jean-Yves, LAHN, Michael, GANDARA, David R, KORALEWSKI, Piotr, MANEGOLD, Christian, SMIT, Egbert F, REYES, José Miguel, CHANG, Gee-Chen, JOHN, William J, PETERSON, Patrick M, OBASAJU, Coleman K
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 20.03.2006; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Cisplatin - administration & dosage; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Disease Progression; Female; Humans; Infusions, Intravenous; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Oligonucleotides, Antisense - administration & dosage; Oligonucleotides, Antisense - therapeutic use; Phosphorothioate Oligonucleotides; Pneumology; Survival Analysis; Tumors; Tumors of the respiratory system and mediastinum; Antineoplastic agent; Phase III trial; Protein kinase A; Protein kinase C; Gemcitabine; Lung cancer; non-small cell lung carcinoma; Aprinocarsen; Cancerology; Bronchus disease; Advanced stage; Pyrimidine nucleoside; Platinum II Complexes; Human; Lung disease; Respiratory disease; Enzyme; Transferases; Malignant tumor; Antisense oligonucleotide; Cisplatin; Alkylating agent; Treatment; Antimetabolic; Pyrimidine derivatives; Fluorine Organic compounds
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2005.04.3299

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 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/m2 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. 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. Adding aprinocarsen to gemcitabine and cisplatin regimen did not enhance survival and other efficacy measures in patients with advanced NSCLC.