Adenovirus-mediated p53 gene transfer in sequence with cisplatin to tumors of patients with non-small-cell lung cancer.
J Clin Oncol
; 18(3): 609-22, 2000 Feb.
Article
em En
| MEDLINE
| ID: mdl-10653876
ABSTRACT
PURPOSE:
To determine the safety and tolerability of adenovirus-mediated p53 (Adp53) gene transfer in sequence with cisplatin when given by intratumor injection in patients with non-small-cell lung cancer (NSCLC). PATIENTS ANDMETHODS:
Patients with advanced NSCLC and abnormal p53 function were enrolled onto cohorts receiving escalating dose levels of Adp53 (1 x 10(6) to 1 x 10(11) plaque-forming units [PFU]). Patients were administered intravenous cisplatin 80 mg/m(2) on day 1 and study vector on day 4 for a total of up to six courses (28 days per course). Apoptosis was determined by the terminal deoxynucleotidyl- transferase-dUTP nick-end labeling assay. Evidence of vector-specific sequences were determined using reverse-transcriptase polymerase chain reaction. Vector dissemination and biodistribution was monitored using a series of assays (cytopathic effects assay, Ad5 hexon enzyme-linked immunosorbent assay, vector-specific polymerase chain reaction assay, and antibody response assay).RESULTS:
Twenty-four patients (median age, 64 years) received a total of 83 intratumor injections with Adp53. The maximum dose administered was 1 x 10(11) PFU per dose. Transient fever related to Adp53 injection developed in eight of 24 patients. Seventeen patients achieved a best clinical response of stable disease, two patients achieved a partial response, four patients had progressive disease, and one patient was not assessable. A mean apoptotic index between baseline and follow-up measurements increased from 0.010 to 0.044 (P =.011). Intratumor transgene mRNA was identified in 43% of assessable patients.CONCLUSION:
Intratumoral injection with Adp53 in combination with cisplatin is well tolerated, and there is evidence of clinical activity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Genes p53
/
Cisplatino
/
Técnicas de Transferência de Genes
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Carcinoma Pulmonar de Células não Pequenas
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Neoplasias Pulmonares
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Antineoplásicos
Limite:
Adult
/
Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article