CT-guided intratumoral gene therapy in non-small-cell lung cancer

The objective of this study was to prove the principle of CT-guided gene th erapy by intratumoral injection of a tumor suppressor gene as an alternativ e treatment approach of incurable non-small-cell lung cancer. In a prospect ive clinical phase I trial six patients with non-small-cell lung cancer and a mutation of the tumor suppressor gene p53 were treated by CT-guided intr atumoral gene therapy. Ten milliliters of a vector solution (replication-de fective adenovirus with complete wild-type p53 cDNA) were injected under CT guidance. In four cases the vector solution was completely applied to the tumor center, whereas in two cases 2 ml aliquots were injected into differe nt tumor areas. For the procedure the scan room had been approved as a bios afety cabinet. Gene transfer was assessed by reverse transcription and poly merase chain reaction in biopsy specimens obtained under CT guidance 24-48 h after therapy. Potential therapeutic efficacy was evaluated on day 28 aft er treatment using spiral CT. The CT-guided gene therapy! was easily perfor med in all six patients without intervention-related complications. Besides flu-like symptoms, no significant adverse effects of gene therapy were not ed. Three of the four patients with central injection exhibited gene transf er in the posttreatment biopsy. Gene transfer could not be proven in the tw o patients with multiple 2 ml injections. After 28 days, four of the six pa tients showed stable disease at the treated tumor site, whereas other tumor manifestations progressed. Computed tomography-guided injections are an ad equate and easy-to-perform procedure for intratumoral gene therapy.