Thymidine kinase (TK) gene therapy of solid tumors: Valacyclovir facilitates outpatient treatment

Background: In a Phase I study replication-deficient adenovirus containing the herpes simplex virus (HSV) thymidine kinase (TK) gene (AdV-HSV-TK) was instilled intraperitoneally in patients with recurrent ovarian cancer. Pati ents were treated with Acyclovir (ACV) or Valacyclovir (VCV) as enzymatic s ubstrates. The purpose of this study was to compare serum levels of ACV and VCV. Patients and Methods: The antiherpetic prodrug and Topotecan (1.0 mg/ m(2) over 30 minutes each day for 5 days) were started 24 hours after vecto r application. Eight patients received ACV (15 mg/kg IV over one hour every 8 hours for 42 doses), two patients were started on ACV for 5 days and the n switched to oral VCV (2 g every 8 hours for a total of 42 doses). Blood s amples were obtained 20 minutes prior to each drug. Results: Serum levels o f ACV and VCV (converted to ACV) were comparable. Conclusions: Suicide gene therapy with TK( is under investigation in a variety of solid tumors. Repl acing ACV by VCV will offer a cost-effective alternative and will significa ntly reduce duration of hospital stay improving quality of life and facilit ating art outpatient gene therapy concept.