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

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

journal_name

Gynecol Oncol

journal_title

Gynecologic oncology

authors

Hasenburg A,Tong XW,Fischer DC,Rojas-Martinez A,Nyberg-Hoffman C,Kaplan AL,Kaufman RH,Ramzy I,Aguilar-Cordova E,Kieback DG

doi

10.1006/gyno.2001.6442

subject

Has Abstract

pub_date

2001-12-01 00:00:00

pages

549-54

issue

3

eissn

0090-8258

issn

1095-6859

pii

gyno.2001.6442

journal_volume

83

pub_type

临床试验,杂志文章
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    abstract::Copyright ...

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