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

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 < or =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 x 10(10) vector particles (VP)), dose level 2 (2 x 10(11) VP), and dose level 3 (2 x 10(12) VP); four patients were treated on dose level 4 (2 x 10(13) 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.