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


CONCLUSIONS
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.
Hasenburg
A
A
Department of Obstetrics and Gynecology, Freiburg University Medical Center, Freiburg, Germany.
Tong
X W
XW
Fischer
D C
DC
Rojas-Martinez
A
A
Nyberg-Hoffman
C
C
Kaplan
A L
AL
Kaufman
R H
RH
Ramzy
I
I
Aguilar-Cordova
E
E
Kieback
D G
DG
D000212:Acyclovir / Q000493:pharmacokinetics / Q000627:therapeutic use; D000256:Adenoviridae / Q000201:enzymology / Q000235:genetics; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000601:surgery / Q000628:therapy*; D024162:Second-Look Surgery; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism; D019772:Topotecan / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D019772:Topotecan; D013937:Thymidine Kinase; D000212:Acyclovir