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SUICIDE GENE THERAPY TOXICITY AFTER MULTIPLE AND REPEAT INJECTIONS IN PATIENTS WITH LOCALIZED PROSTATE CANCER

2000; Lippincott Williams & Wilkins; Volume: 163; Issue: 6 Linguagem: Inglês

10.1016/s0022-5347(05)67534-9

1527-3792

Moshe Shalev, Dov Kadmon, Bin S. Teh, E. Brian Butler, Estuardo Aguilar-Córdova, Timothy C. Thompson, James R. Herman, Howard L. Adler, Peter T. Scardino, Brian J. Miles,

Virus-based gene therapy research

No AccessJournal of UrologyCLINICAL UROLOGY: Original Articles1 Jun 2000SUICIDE GENE THERAPY TOXICITY AFTER MULTIPLE AND REPEAT INJECTIONS IN PATIENTS WITH LOCALIZED PROSTATE CANCER MOSHE SHALEV, DOV KADMON, BIN S. TEH, EDWARD B. BUTLER, ESTUARDO AGUILAR-CORDOVA, TIMOTHY C. THOMPSON, JAMES R. HERMAN, HOWARD L. ADLER, PETER T. SCARDINO, and BRIAN J. MILES MOSHE SHALEVMOSHE SHALEV More articles by this author , DOV KADMONDOV KADMON More articles by this author , BIN S. TEHBIN S. TEH More articles by this author , EDWARD B. BUTLEREDWARD B. BUTLER More articles by this author , ESTUARDO AGUILAR-CORDOVAESTUARDO AGUILAR-CORDOVA More articles by this author , TIMOTHY C. THOMPSONTIMOTHY C. THOMPSON More articles by this author , JAMES R. HERMANJAMES R. HERMAN More articles by this author , HOWARD L. ADLERHOWARD L. ADLER More articles by this author , PETER T. SCARDINOPETER T. SCARDINO More articles by this author , and BRIAN J. MILESBRIAN J. MILES More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)67534-9AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We assess risks, toxicity and side effects of multiple and repeat in situ suicide gene therapy in patients with localized prostate cancer. Materials and 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. References 1 : Inhibition of cell proliferation by an adenovirus vector expressing the human wild type p53 protein. Int J Oncol1993; 3: 781. Google Scholar 2 : Development and characterization of recombinant adenovirus encoding human p53 for gene therapy of cancer. Hum Gene Ther1994; 5: 1079. Google Scholar 3 : High-efficiency gene transfer and high-level expression of wild-type p53 in human lung cancer cells mediated by recombinant adenovirus. Cancer Gene Ther1994; 1: 5. Google Scholar 4 : Molecular therapy with recombinant p53 adenovirus in an androgen-independent, metastatic human prostate cancer model. Hum Gene Ther1996; 7: 1683. Google Scholar 5 : Immunotherapy of prostate cancer in the Dunning rat model: use of cytokine gene modified tumor vaccines. Cancer Res1994; 54: 1760. 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Google Scholar From the Matsunaga-Conte Prostate Cancer Research Center, Scott Department of Urology, and Departments of Radiology, Cell Biology and Pediatrics, Baylor College of Medicine and Gene Vector Laboratory, and Texas Children’s Cancer Center, Texas Children’s Hospital, Houston, Texas© 2000 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited bySteinberg G, Rinker-Schaeffer C, Sokoloff M and Brendler C (2018) Highlights Of The Society Of Urologic Oncology Meeting, June 2, 2001Journal of Urology, VOL. 168, NO. 2, (653-659), Online publication date: 1-Aug-2002.Ratliff T (2018) URO-SCIENCEJournal of Urology, VOL. 167, NO. 5, (2327-2330), Online publication date: 1-May-2002.HARRINGTON K, SPITZWEG C, BATEMAN A, MORRIS J and VILE R (2018) GENE THERAPY FOR PROSTATE CANCER: CURRENT STATUS AND FUTURE PROSPECTSJournal of Urology, VOL. 166, NO. 4, (1220-1233), Online publication date: 1-Oct-2001. Volume 163Issue 6June 2000Page: 1747-1750 Advertisement Copyright & Permissions© 2000 by American Urological Association, Inc.Keywordsprostateprostatic neoplasmsgene therapygancicloviradenoviridaeMetricsAuthor Information MOSHE SHALEV More articles by this author DOV KADMON More articles by this author BIN S. TEH More articles by this author EDWARD B. BUTLER More articles by this author ESTUARDO AGUILAR-CORDOVA More articles by this author TIMOTHY C. THOMPSON More articles by this author JAMES R. HERMAN More articles by this author HOWARD L. ADLER More articles by this author PETER T. SCARDINO More articles by this author BRIAN J. MILES More articles by this author Expand All Advertisement PDF downloadLoading ...