Adenovirus-Mediated p53 Gene Transfer in Sequence With Cisplatin to Tumors of Patients With Non–Small-Cell Lung Cancer

• DOI: 10.1200/jco.2000.18.3.609
• Publication Date: 2017-02-24T07:04:24Z
• Authors: J. Nemunaitis; S.G. Swisher; T. Timmons; D. Connors; M. Mack; L. Doerksen; D. Weill; J. Wait; D.D. Lawrence; B.L. Kemp; F. Fossella; B.S. Glisson; W.K. Hong; F.R. Khuri; J.M. Kurie; J.J. Lee; J.S. Lee; D.M. Nguyen; J.C. Nesbitt; R. Perez-Soler; K.M. W. Pisters; J.B. Putnam; W.R. Richli; D.M. Shin; G.L. Walsh; J. Merritt; J. Roth
• Keywords: Tolerability

To determine the safety and tolerability of adenovirus-mediated p53 (Adp53) gene transfer in sequence with cisplatin when given by intratumor injection patients non-small-cell lung cancer (NSCLC).Patients advanced NSCLC abnormal function were enrolled onto cohorts receiving escalating dose levels Adp53 (1 x 10(6) to 1 10(11) plaque-forming units [PFU]). Patients administered intravenous 80 mg/m(2) on day study vector 4 for a total up six courses (28 days per course). Apoptosis was determined terminal deoxynucleotidyl- transferase-dUTP nick-end labeling assay. Evidence vector-specific sequences using reverse-transcriptase polymerase chain reaction. Vector dissemination biodistribution monitored series assays (cytopathic effects assay, Ad5 hexon enzyme-linked immunosorbent reaction antibody response assay).Twenty-four (median age, 64 years) received 83 injections Adp53. The maximum PFU dose. Transient fever related developed eight 24 patients. Seventeen achieved best clinical stable disease, two partial response, four had progressive one patient not assessable. A mean apoptotic index between baseline follow-up measurements increased from 0.010 0.044 (P =.011). Intratumor transgene mRNA identified 43% assessable patients.Intratumoral combination is well tolerated, there evidence activity.