Adenoviral-mediated suicide gene therapy for ovarian cancer.
The purpose of this phase I study was to determine the potential efficacy of adenoviral-mediated suicide gene therapy in women with recurrent ovarian cancer. Fourteen patients were treated intraperitoneally with herpes simplex virus-thymidine kinase (HSV-TK)-encoding adenovirus (AdHSV-TK) in dosages ranging between 1x10(9) and 1x10(11) pfu. Beginning 2 days later, ganciclovir (GCV) was administered intravenously at a dose of 5 mg/kg bid for 14 days. Transient vector-associated fever was experienced by 4 of 14 (29%) treated patients. Other possible vector-associated constitutional symptoms, abdominal pain, and gastrointestinal symptoms were experienced by 6 of 14 (43%) treated patients. No other dose-limiting vector-specific side effects were noted. Of the 13 patients evaluable for response, 5 (38%) had stable disease and 8 (62%) had evidence of progressive disease. Molecular analysis of evaluable ascites samples demonstrated the presence of transgene DNA and RNA in most patients 2 days following Ad HSV-TK administration. Ten of 11 evaluable patients had an increase in anti-adenovirus antibody titer. These results suggest that treatment with AdHSV-TK in combination with GCV is feasible in the context of human ovarian cancer and tolerated at the dosages studied.
Alvarez
R D
RD
Department of Obstetrics and Gynecology, National Gene Vector Laboratory, Birmingham, Alabama 35233, USA. rdalvarez@aol.com
Gomez-Navarro
J
J
Wang
M
M
Barnes
M N
MN
Strong
T V
TV
Arani
R B
RB
Arafat
W
W
Hughes
J V
JV
Siegal
G P
GP
Curiel
D T
DT
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D004279:DNA, Viral / Q000032:analysis; D004334:Drug Administration Schedule; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage*; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000009:adverse effects; D006801:Humans; D007274:Injections, Intraperitoneal; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics*; D013937:Thymidine Kinase / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D019076:Transgenes
D000914:Antibodies, Viral; D004279:DNA, Viral; D013937:Thymidine Kinase; D015774:Ganciclovir