Management of resistant lung cancer malignant pleural effusion by intrapleural gene therapy

Abstract

3168 Background: Cytosine deaminase, transferred into tumour cells by an adenovirus vector, can convert the antifungal drug flucytosine to the antimetabolite 5-fluorouracil, which kills not only the transfected tumour cells but also their neighbours by the so-called ‘bystander’ effect. We used this technique in the management of lung cancer patients with malignant pleural effusion Methods: We used this technique in the management of six lung cancer patients with malignant pleural effusion, confirmed either histologically or pathologically. Two patients suffered from small cell lung cancer, which had relapsed after completion of initial chemotherapy, and four patients from adenocarcinoma of the lung that had progressed during chemotherapy procedure. The pleural fluid was drained through intercostal tube, and the treatment procedure was performed when the daily fluid production was less than 200 ml. A total amount of 1012 pfu of adenovirus vector was instilled into the pleural cavity either in a single dose (in four patients) or in two fractions (in two patients, given on the 1st and 7th day). All patients received flucytosine (Ancotil - Roche) 500 mg qds for 14 days Results: In two of the six patients reaccumulation of the fluid stopped within two weeks (one with an adenocarcinoma and the other with SCLC -treatment only by AdCD) and the drain was removed. These two patients died (after 3 and 22 months respectively) because of disease progression without evidence of pleural effusion. The main constitutional toxicity in all patients was fever due to the AdCD. Three patients experienced grade 3 neutropenia due to the concurrently given chemotherapy Conclusions: Intrapleural gene therapy may be a useful adjunct to chemotherapy in the management of refractory pleural effusions associated with lung cancer. No significant financial relationships to disclose.