title: 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.affiliation: Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Vansteenkiste
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Canon
authors.forename: Henrik
authors.initials: H
authors.lastname: Riska
authors.forename: Robert
authors.initials: R
authors.lastname: Pirker
authors.forename: Patrick
authors.initials: P
authors.lastname: Peterson
authors.forename: William
authors.initials: W
authors.lastname: John
authors.forename: Pekka
authors.initials: P
authors.lastname: Mali
authors.forename: Michael
authors.initials: M
authors.lastname: Lahn
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage; D054735:Phosphorothioate Oligonucleotides; D000093542:Gemcitabine
chemical_list: D016376:Oligonucleotides, Antisense; D054735:Phosphorothioate Oligonucleotides; D003841:Deoxycytidine; C488084:aprinocarsen; D002945:Cisplatin; D000093542:Gemcitabine