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Thymidine kinase gene therapy with concomitant topotecan chemotherapy for recurrent ovarian cancer

Abstract

Introduction: Patients with recurrent ovarian cancer were treated with a replication-deficient recombinant adenovirus containing the herpes simplex virus thymidine kinase gene administered intraperitoneally (i.p.) followed by administration of an anti-herpetic prodrug and topotecan.

Materials and Methods: A total of 10 patients with stage IIIc epithelial ovarian cancer underwent secondary debulking to ≤0.5 cm residual tumor. Patients with normal i.p. flow received i.p. delivery of adenovirus. Two patients each were treated on dose level 1 (2 × 1010 vector particles (VP)), dose level 2 (2 × 1011 VP), and dose level 3 (2 × 1012 VP); four patients were treated on dose level 4 (2 × 1013 VP). Acyclovir and topotecan were started 24 hours after vector delivery.

Results: No patient treated at any dose level incurred unanticipated toxic effects, and all side effects resolved. The most common adverse event was myelosuppression: grade 3 or 4 thrombocytopenia with grade 2–4 anemia in three patients and grade 3 or 4 neutropenia in eight patients. Three patients developed thrombocytosis and three patients had a mild elevation of serum glutamic pyruvic transaminase/alanine aminotransferase. Temperature elevations that were not associated with detectable infection occurred in two patients.

Discussion: I.p. delivery of adenoviral vector with concomitant topotecan chemotherapy was well tolerated without significant lasting toxicities. Side effects were independent of the dose of adenoviral vector.

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Correspondence to Dirk G Kieback.

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Hasenburg, A., Tong, XW., Rojas-Martinez, A. et al. Thymidine kinase gene therapy with concomitant topotecan chemotherapy for recurrent ovarian cancer. Cancer Gene Ther 7, 839–844 (2000). https://doi.org/10.1038/sj.cgt.7700192

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  • DOI: https://doi.org/10.1038/sj.cgt.7700192

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