ID | 13215 |
Sort Key | 2
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Title Alternative | Adenoviral p53 gene therapy for lung cancer
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FullText URL | |
Author |
Tanaka, Noriaki
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Abstract | To determine the feasibility, safety, humoral immune response, and biological activity of multiple intratumoral injections of Ad5CMV-p53, and to characterize the pharmacokinetics of Ad5CMV-p53 in patients with advanced non-small cell lung cancer (NSCLC). Fifteen patients with histologically confirmed NSCLC and p53 mutations were enrolled into this phase I trial. Nine patients received escalating dose levels of Ad5CMV-p53 (1 × 109 to 1 × 1011 plaque-forming units[PFU]) as monotherapy once every 4 weeks. Six patients were treated on a 28-day schedule with Ad5CMV-p53 in combination with intravenous administration of cisplatin (80 mg/m2). Patients were monitored for toxicity, vector distribution, antibody formation, and tumor response. Fifteen patients received a total of 63 intratumoral injections of Ad5CMV-p53 without dose-limiting toxicity. The most common treatment-related toxicity was a transient fever. Specific p53 transgene expression was detected using reverse-transcriptase polymerase chain reaction in biopsied tumor tissues throughout the period of treatment despite of the presence of neutralizing anti-adenovirus antibody. Distribution studies revealed that the vector was detected in the gargle and plasma, but rarely in the urine. Thirteen of 15 patients were assessable for efficacy; one patient had a partial response (squamous cell carcinoma at the carina), 10 patients had stable disease, with three lasting ≥9 months, and 2 patients had progressive disease. Multiple courses of intratumoral Ad5CMV-p53 injection alone or in combination with intravenous administration of cisplatin were feasible and well tolerated in advanced NSCLC patients, and appeared to provide clinical benefit.
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Keywords | p53 遺伝子
アデノウイルスベクター (adenovirus vector)
肺癌 (lung cancer)
臨床試験 (clinical trial)
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Note | 平成18年度岡山医学会賞(林原賞)受賞論文
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Publication Title |
岡山医学会雑誌
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Published Date | 2008-01-04
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Volume | volume119
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Issue | issue3
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Publisher | 岡山医学会
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Publisher Alternative | Okayama Medical Association
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Start Page | 229
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End Page | 234
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ISSN | 00301558
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NCID | AN00032489
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Content Type |
Journal Article
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OAI-PMH Set |
岡山大学
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language |
Japanese
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Copyright Holders | 岡山医学会
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File Version | publisher
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Refereed |
True
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DOI | |
NAID | |
Eprints Journal Name | joma
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