Adenovirus-mediated thymidine kinase gene therapy in combination with topotecan for patients with recurrent ovarian cancer: 2.5-Year follow-up

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

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Objective. Patients with recurrent ovarian cancer were treated intraperitoneally (ip) with a replication-deficient recombinant adenovirus (ADV) containing the herpes simplex virus thymidine kinase gene. Vector delivery was followed by intravenous administration of an antiherpetic prodrug and a topoisomerase I inhibitor. Methods. Ten patients with stage IIIc epithelial ovarian cancer underwent secondary debulking to ≤0.5 cm residual tumor. Patients with normal ip flow received delivery of ip ADV. Two patients each were treated on dose level 1 (2 × 1010 vector particles), dose level 2 (2 × 1011), and dose level 3 (2 × 1012); four patients were on dose level 4 (2 × 1013). Acyclovir and topotecan were started 24 h after vector delivery. Five patients underwent second-look surgery about 4 weeks after application of gene therapy (GT). Results. At the time of the second-look surgery, two out of five patients were free of tumor. Four weeks after GT none of the peritoneal biopsies showed residual vector DNA. Patients pre-treated with an average of three different chemotherapeutic drugs and two different chemotherapy regimens had a median overall survival (OS) of 18.5 months. Three patients are still alive 30, 30, and 31 months after GT. Conclusion. With the combination of secondary optimal debulking, GT, and topotecan, median OS was about one-third longer than in previously reported second-and third-line trials. Survival was comparable to that of patients of other studies with secondary cytoreductive surgery in combination with chemotherapy.

Original languageEnglish (US)
Pages (from-to)549-554
Number of pages6
JournalGynecologic oncology
Volume83
Issue number3
DOIs
StatePublished - Jan 1 2001

Keywords

  • Intraperitoneal therapy
  • Recurrent ovarian cancer
  • Survival
  • Thymidine kinase gene therapy

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

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