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.
OBJECTIVE
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).


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/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.


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.


CONCLUSIONS
Adding aprinocarsen to gemcitabine and cisplatin regimen did not enhance survival and other efficacy measures in patients with advanced NSCLC.
Paz-Ares
Luis
L
Servicio de Oncología Médica, Doce de Octubre University Hospital, Madrid, Spain. lpaz.hdoc@salud.madrid.org
Douillard
Jean-Yves
JY
Koralewski
Piotr
P
Manegold
Christian
C
Smit
Egbert F
EF
Reyes
José Miguel
JM
Chang
Gee-Chen
GC
John
William J
WJ
Peterson
Patrick M
PM
Obasaju
Coleman K
CK
Lahn
Michael
M
Gandara
David R
DR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000627:therapeutic use*; D054735:Phosphorothioate Oligonucleotides; D016019:Survival Analysis; D000093542:Gemcitabine
D016376:Oligonucleotides, Antisense; D054735:Phosphorothioate Oligonucleotides; D003841:Deoxycytidine; C488084:aprinocarsen; D002945:Cisplatin; D000093542:Gemcitabine