title: Suicide gene therapy toxicity after multiple and repeat injections in patients with localized prostate cancer.
abstract: OBJECTIVE
  We assess risks, toxicity and side effects of multiple and repeat in situ suicide gene therapy in patients with localized prostate cancer.
  
  
  METHODS
  The study population comprised patients with localized prostate cancer receiving multiple and/or repeat intraprostatic injections of a replication deficient adenovirus containing the herpes simplex virus thymidine kinase (HSV-tk) gene. Intravenous ganciclovir or oral valaciclovir was given for 14 days after injection. Patients were recruited from 4 different clinical protocols in studies of toxicity and efficacy of suicide gene therapy, and closely monitored for toxicity and side effects during and after treatment. Toxicity was graded according to the Cancer Therapy Evaluation Program common toxicity criteria published by the National Cancer Institute.
  
  
  RESULTS
  A total of 52 patients were treated under these clinical protocols with a total of 76 gene therapy cycles. Toxic events were recorded in 16 of 29 patients (55.2%) who were given multiple viral injections into the prostate, 7 of 20 (35%) who received 2 cycles of "suicide" gene therapy and 3 of 4 (75%) who received a third course of gene therapy. All toxic events after multiple or repeat injections were mild (grades 1 to 2) and resolved completely once the therapy course was terminated. No additive toxicity was noted in patients receiving repeat gene therapy cycles. Mean followup was 12.8 months (range 3 to 34). Preliminary results for 28 patients in 2 clinical protocols indicated a mean decrease of 44% in PSA in 43%.
  
  
  CONCLUSIONS
  Direct injection into the prostate of a replication defective adenovirus containing the HSV-tk gene followed by intravenous ganciclovir is safe even in repeat cycles.
authors.affiliation: Matsunaga-Conte Prostate Cancer Research Center, Scott Department of Urology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: M
authors.initials: M
authors.lastname: Shalev
authors.forename: D
authors.initials: D
authors.lastname: Kadmon
authors.forename: B S
authors.initials: BS
authors.lastname: Teh
authors.forename: E B
authors.initials: EB
authors.lastname: Butler
authors.forename: E
authors.initials: E
authors.lastname: Aguilar-Cordova
authors.forename: T C
authors.initials: TC
authors.lastname: Thompson
authors.forename: J R
authors.initials: JR
authors.lastname: Herman
authors.forename: H L
authors.initials: HL
authors.lastname: Adler
authors.forename: P T
authors.initials: PT
authors.lastname: Scardino
authors.forename: B J
authors.initials: BJ
authors.lastname: Miles
mesh_terms: D000212:Acyclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D000256:Adenoviridae / Q000235:genetics*; D000998:Antiviral Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003673:Defective Viruses / Q000235:genetics*; D015774:Ganciclovir / Q000627:therapeutic use; D015316:Genetic Therapy / Q000009:adverse effects*; D005822:Genetic Vectors; D006801:Humans; D015552:Injections, Intralesional; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000628:therapy* / Q000821:virology; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D013937:Thymidine Kinase; D014633:Valine; D000077483:Valacyclovir; D015774:Ganciclovir; D000212:Acyclovir