THE TREATMENT OF MALIGNANT MESOTHELIOMA WITH A GENE MODIFIED CANCER CELL-LINE - A PHASE-I STUDY

Malignant mesothelioma is a tumor of the pleura for which there is no satisfactory treatment. It is almost universally fatal, regardless of the stage of the tumor at the time of diagnosis. Current treatment mod alities include surgery, chemotherapy, and radiation therapy, although in some series none of these modalities is superior to no treatment a t all. Because of the dismal prognosis for patients with malignant mes othelioma, a new mode of treatment is desperately needed. A promising area of research into the treatment of various malignancies is gene th erapy. Recent studies have demonstrated the utility of exposing tumor cells to cells transduced to express the Herpes simplex virus gene for thymidine kinase (HSV-tk). By virtue of their expression of HSV-tk, t he transduced cells are rendered susceptible to the antiviral drug, ga nciclovir (GCV), and nearby tumor cells are killed by a phenomenon ter med the bystander effect. In this protocol we propose a Phase I trial to study the safety and determine the maximal tolerated dose of an HSV -tk-transduced ovarian cancer cell line (PA1-STK cells) infused into t he pleural cavities of patients with malignant pleural mesothelioma, f ollowed by systemic administration of,ganciclovir. The hope is that ad ministration of ganciclovir will result in killing of the HSV-tk trans duced ovarian cancer cells as well as the nearby malignant mesotheliom a cells. This is a standard dose-escalation protocol.