Thymidine kinase (TK) gene therapy of solid tumors: valacyclovir facilitates outpatient treatment.
BACKGROUND
In a Phase I study replication-deficient adenovirus containing the herpes simplex virus (HSV) thymidine kinase (TK) gene (AdV-HSV-TK) was instilled intraperitoneally in patients with recurrent ovarian cancer. Patients were treated with Acyclovir (ACV) or Valacyclovir (VCV) as enzymatic substrates. The purpose of this study was to compare serum levels of ACV and VCV.


METHODS
The antiherpetic prodrug and Topotecan (1.0 mg/m2 over 30 minutes each day for 5 days) were started 24 hours after vector application. Eight patients received ACV (15 mg/kg i.v. over one hour every 8 hours for 42 doses), two patients were started on ACV for 5 days and then switched to oral VCV (2 g every 8 hours for a total of 42 doses). Blood samples were obtained 20 minutes prior to each drug.


RESULTS
Serum levels of ACV and VCV (converted to ACV) were comparable.


CONCLUSIONS
Suicide gene therapy with TK is under investigation in a variety of solid tumors. Replacing ACV by VCV will offer a cost-effective alternative and will significantly reduce duration of hospital stay improving quality of life and facilitating an outpatient gene therapy concept.
Hasenburg
A
A
Department of Obstetrics and Gynecology, Freiburg University Medical Center, Germany.
Tong
X W
XW
Rojas-Martinez
A
A
Nyberg-Hoffman
C
C
Kieback
C C
CC
Kaplan
A L
AL
Kaufman
R H
RH
Ramzy
I
I
Aguilar-Cordova
E
E
Kieback
D G
DG
D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use*; D000284:Administration, Oral; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D015316:Genetic Therapy / Q000009:adverse effects; D006801:Humans; D007322:Instillation, Drug; D010045:Outpatients; D010051:Ovarian Neoplasms / Q000628:therapy*; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics*; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use
D000998:Antiviral Agents; D011355:Prodrugs; D013937:Thymidine Kinase; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir