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

A. Hasenburg, X. W. Tong, A. Rojas-Martinez, C. Nyberg-Hoffman, C. C. Kieback, Alan L. Kaplan, R. H. Kaufman, I. Ramzy, E. Aguilar-Cordova, Dirk G. Kieback

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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. Patients were treated with Acyclovir (ACV) or Valacyclovir (VCV) as enzymatic substrates. 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/m2 over 30 minutes each day for 5 days) were started 24 hours after vector 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 then switched to oral VCV (2 g every 8 hours for a total of 42 doses). Blood samples were obtained 20 minutes prior to each drug. Results: Serum levels of ACV and VCV (converted to ACV) were comparable. Conclusions: Suicide gene therapy with TK is under investigation in a variety of solid tumors. Replacing ACV by VCV will offer a cost-effective alternative and will significantly reduce duration of hospital stay improving quality of life and facilitating an outpatient gene therapy concept.

Original languageEnglish (US)
Pages (from-to)2163-2165
Number of pages3
JournalAnticancer Research
Volume19
Issue number3 B
StatePublished - Aug 30 1999

Keywords

  • Acyclovir
  • Gene therapy
  • Intraperitoneal therapy
  • Ovarian cancer
  • Valacyclovir

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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