The purpose of this study was to determine the feasability and utility of adenoviral mediated suicide gene therapy in women with recurrent ovarian cancer. A phase I trial was conducted in women with recurrent intraperitoneal ovarian cancer. Adenovirus encoding Herpes simplex virus-thymidine kinase (AdHSF-TK) was administered intraperitoneally through a percutaneous Tenckhoff catheter; the dose of AdHSV-TK was escalated in cohorts of patients between 1 x 10(9) pfu. Two days later, patients were treated with intravenous ganciclovir (GCV) at a dose of 5 mg/kg BID for a total of 14 days. Patients were monitored at regular intervals for eight weeks post-treatment for evidence of clinical toxicity and response. Serum samples and peritoneal aspirates were obtained at various time points to assess for evidence of gene transfer and immunologic response. Fourteen patients with persistent/recurrent ovarian cancer were treated per study specifications. Most patients had been extensively treated with a variety of chemotherapy regimens. Transient and easily ameliorated vector-associated fever was experienced by 4/14(29%) of treated patients. Other possible vector-associated constitutional (fatigue, insomnia) symptoms, abdominal pain, and gastrointestinal (nausea, diarrhea) symptoms were experienced by 6 of 14 (43%) treated patients. No other vector specific side effects were noted. Six patients experienced catheter-associated complications (infection-5, partial bowel obstruction-1). One patient expired due to a pulmonary embolism three weeks post therapy.
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