International Journal of Radiation Oncology * Biology * Physics
Volume 51, Issue 3 , Pages 605-613 , 1 November 2001

Phase I/II trial evaluating combined radiotherapy and in situ gene therapy with or without hormonal therapy in the treatment of prostate cancer—A preliminary report

Presented at ASTRO’s 42nd Annual Meeting, 22–26 October, 2000, Boston, Massachusetts.

  • Bin S. Teh, M.D.

      Affiliations

    • Department of Radiology/Section of Radiation Oncology, Houston, TX, USA
  • ,
  • Estuardo Aguilar-Cordova, Ph.D.

      Affiliations

    • Department of Radiology/Section of Radiation Oncology, Houston, TX, USA
    • Department of Cell Biology and Gene Therapy, Houston, TX, USA
  • ,
  • Kenneth Kernen, M.D.

      Affiliations

    • Department of Urology, Houston, TX, USA
  • ,
  • Chieng-Chung Chou, M.D.

      Affiliations

    • Department of Radiology/Section of Radiation Oncology, Houston, TX, USA
  • ,
  • Moshe Shalev, M.D.

      Affiliations

    • Department of Urology, Houston, TX, USA
  • ,
  • Maria T. Vlachaki, M.D.

      Affiliations

    • Department of Radiology/Section of Radiation Oncology, Houston, TX, USA
  • ,
  • Brian Miles, M.D.

      Affiliations

    • Department of Urology, Houston, TX, USA
  • ,
  • Dov Kadmon, M.D.

      Affiliations

    • Department of Urology, Houston, TX, USA
  • ,
  • Wei-Yuan Mai, M.D.

      Affiliations

    • Department of Radiology/Section of Radiation Oncology, Houston, TX, USA
  • ,
  • James Caillouet, R.T.T.

      Affiliations

    • Department of Radiation Therapy, The Methodist Hospital, Houston, TX, USA
  • ,
  • Maria Davis, R.N.

      Affiliations

    • Department of Radiation Therapy, The Methodist Hospital, Houston, TX, USA
  • ,
  • Gustavo Ayala, M.D.

      Affiliations

    • Department of Pathology, Baylor College of Medicine, Houston, TX, USA
  • ,
  • Thomas Wheeler, M.D.

      Affiliations

    • Department of Pathology, Baylor College of Medicine, Houston, TX, USA
  • ,
  • Jett Brady, M.D.

      Affiliations

    • Department of Radiology/Section of Radiation Oncology, Houston, TX, USA
  • ,
  • L.Steve Carpenter, M.D.

      Affiliations

    • Department of Radiology/Section of Radiation Oncology, Houston, TX, USA
  • ,
  • Hsin H. Lu, M.D.

      Affiliations

    • Department of Radiology/Section of Radiation Oncology, Houston, TX, USA
  • ,
  • J.Kam Chiu, M.D.

      Affiliations

    • Department of Radiology/Section of Radiation Oncology, Houston, TX, USA
  • ,
  • Shiao Y. Woo, M.D.

      Affiliations

    • Department of Radiology/Section of Radiation Oncology, Houston, TX, USA
  • ,
  • Timothy Thompson, Ph.D.

      Affiliations

    • Department of Radiology/Section of Radiation Oncology, Houston, TX, USA
    • Department of Cell Biology and Gene Therapy, Houston, TX, USA
    • Department of Urology, Houston, TX, USA
  • ,
  • E.Brian Butler, M.D.

      Affiliations

    • Department of Radiology/Section of Radiation Oncology, Houston, TX, USA
    • Some of the authors have moved prior to the publication of this paper. Their current affiliations are as follows: Estuardo Aguilar-Cordova, Ph.D.—Gene Therapy Initiative, Harvard Medical School, Boston, MA; Kenneth M. Kernen, M.D.—Michigan Institute of Urology, Detroit, MI; Chieng-Chung Chou, M.D.—Chang Gung University and Memorial Hospital, Taiwan; and Moshe Shalev, M.D.—Dept. of Urology, Meir General Hospital, Kfar-Saba, Israel.
    • Corresponding Author InformationReprint requests to: E. Brian Butler, M.D., The Methodist Hospital Radiation Therapy Department, 6565 Fannin, MS 121-B, Houston, TX 77030. Tel: (713) 790-2637; Fax: (713) 793-1300

Received 13 December 2000 ,Revised 14 May 2001 ,Accepted 19 May 2001.

References 

  1. Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer statistics, 2000. CA Cancer J Clin. 2000;50(1):7–33
  2. Hanks GE, Lee WR, Hanlon AL, et al.  Conformal technique dose escalation for prostate cancer (Biochemical evidence of improved cancer control with higher doses in patients with pre-treatment prostate-specific antigen > 10 ng/ml)). Int J Radiat Oncol Biol Phys. 1996;35:862–868
  3. Pollack A, Zagars GK. External beam radiotherapy dose response of prostate cancer. Int J Radiat Oncol Biol Phys. 1997;39(5):1011–1018
  4. Smit WGJM, Helle PA, Van Putten WLJ, et al.  Late radiation damage in prostate cancer patients treated by high dose external radiotherapy in relation to rectal dose. Int J Radiat Oncol Biol Phys. 1990;18:23–29
  5. Lawton CA, Wonb M, Pilepich MV, et al.  Long-term treatment sequelae following external beam irradiation for adenocarcinoma of the prostate (Analysis of RTOG studies 7506 and 7706). Int J Radiat Oncol Biol Phys. 1991;21:935–939
  6. Sikora K, Pandha H. Gene therapy for prostate cancer. Br J Urol. 1997;79:64–68
  7. Fyfe JA, Keller PM, Furman PA, et al.  Thymidine kinase from herpes simplex virus phosphorylates the new antiviral compound, 9-(2-hydroxyethoxymethyl) guanine. J Biol Chem. 1978;253:8721–8727
  8. Eastham JA, Chen S-H, Sehgal I, et al.  Prostate cancer gene therapy (Herpes simplex virus thymidine kinase gene transduction followed by ganciclovir in mouse and human prostate cancer models). Hum Gene Ther. 1996;7:515–523
  9. Hall SJ, Mutchnik SE, Chen S-H, et al.  Adenovirus-mediated herpes simplex virus thymidine kinase gene and ganciclovir therapy leads to systemic activity against spontaneous and induced metastasis in an orthotopic mouse model of prostate cancer. Int J Cancer. 1997;70:183–187
  10. Herman JR, Adler HL, Aguilar-Cordova E, et al.  In situ gene therapy for adenocarcinoma of the prostate (A Phase I clinical trial). Hum Gene Ther. 1999;10:1239–1249
  11. Chhikara M, Huang H, Vlachaki MT, et al.  Radio-gene therapy. Enhanced therapeutic effect of HSV-tk+GCV gene therapy and ionizing radiation for prostate cancer. Molecular Therapy. 2001;3(4):536–542
  12. Chen SH, Shine HD, Goodman JC, et al.  Gene therapy for brain tumors (Regression of experimental gliomas by adeno-virus-mediated gene transfer in vivo). Proc Natl Acad Sci U S A. 1994;91:3054–3057
  13. Hasenburg A, Tong XW, Rojas-Martinez A, et al.  Thymidine kinase gene therapy with concomitant topotecan chemotherapy for recurrent ovarian cancer. Cancer Gene Ther. 2000;7(6):839–844
  14. Teh BS, Mai WY, Uhl BM, et al. Intensity-modulated radiation therapy (IMRT) for prostate cancer with the use of a rectal balloon for prostate immobilization: Acute toxicity and dose-volume analysis. Int J Radiat Oncol Biol Phys 2001;49(1) (In press).
  15. Teh BS, Woo SY, Butler EB. Intensity modulated radiation therapy (IMRT) (A new frontier in radiation oncology). The Oncologist. 1999;4:433–442
  16. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995;31:1341–1346
  17. Zietman A. Radiation therapy or prostatectomy (An old conflict revisited in the PSA era. A radiation oncologist’s viewpoint). Semin Radiat Oncol. 1998;8:81–85
  18. Zagars GK, Pollack A, Kavadi VS, et al.  Prostate specific antigen and radiation therapy for clinically localized prostate cancer (An update and review of the MD Anderson experience). Int J Radiat Oncol Biol Phys. 1995;32:293–306
  19. Zietman A, Coen JJ, Shipley WU, et al.  Radical radiation therapy in the management of prostatic adenocarcinoma (The initial prostate specific antigen value as a predictor of treatment outcome). J Urol. 1994;141:640–645
  20. Zelefsky MJ, Liebel SA, Kutcher GJ, et al.  Three-dimensional conformal radiotherapy and dose escalation (Where do we stand?). Semin Radiat Oncol. 1998;8(2):107–114
  21. Hanlon AL, Schultheiss TE, Hunt MA, et al.  Chronic rectal bleeding after high-dose conformal treatment of prostate cancer warrants modification of existing morbidity scales. Int J Radiat Oncol Biol Phys. 1997;38(1):59–63
  22. Pilepich MV, Krall JM, Al-Sarraf M, et al.  Androgen deprivation with radiation therapy compared with radiation therapy alone for locally advanced prostatic carcinoma (A randomized comparative trial of the Radiation Therapy Oncology Group). Urology. 1995;45(4):616–623
  23. Bolla M, Gonzalez D, Warde P, et al.  Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med. 1997;337:295–300
  24. Pilepich MV, Caplan R, Byhardt RW, et al.  Phase III trial of androgen suppression using goserelin in unfavourable-prognosis carcinoma of the prostate treated with definitive radiotherapy (Report of the Radiation Therapy Oncology Group Protocol 8531). J Clin Oncol. 1997;15:1013–1021
  25. Laverdier J, Gomez JL, Cusan L, et al.  Beneficial effect of combination hormonal therapy administered prior and following external beam radiation therapy in localized prostate cancer. Int J Radiat Oncol Biol Phys. 1997;37(2):247–252
  26. Hanks GE, Lu J, Machtay MI. RTOG 9202: A phase 3 trial of the long-term androgen suppression following neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate (Abstract #1284). Presented at the 36th Annual Meeting of the American Society of Clinical Oncology. New Orleans: May 23–23, 2000.
  27. Davidson PJT, Hop W, Kurth KH. Progression in untreated carcinoma of the prostate metastatic to regional lymph nodes (Stage T0–4, N1–3 M0, D1). J Urol. 1995;165:2118–2122
  28. Leibel SA, Fuks Z, Zelefsky MJ, et al.  The effects of local and regional treatment on the metastatic outcome in prostatic carcinoma with pelvic lymph node involvement. Int J Radiat Oncol Biol Phys. 1994;28:7–16
  29. Hanks GE, Buzydlowski J, Sause WT, et al.  Ten-year outcomes for pathologic node-positive patients treated in RTOG 75-06. Int J Radiat Oncol Biol Phys. 1998;40:765–768
  30. Lawton CA, Winter K, Byhardt R, et al.  Androgen suppression plus radiation versus radiation alone for patients with D1 (pN+) adenocarcinoma of the prostate (results based on a national prospective randomized trial, RTOG 85-31). Int J Radiat Oncol Biol Phys. 1997;38:931–939
  31. Moolten FL. Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes (Paradigm for a prospective cancer control strategy). Cancer Res. 1986;46:5276–5281
  32. Moolten FL, Wells JM. Curability of tumors bearing herpes thymidine kinase transferred by retroviral vectors. J Natl Cancer Inst. 1990;82:297–300
  33. Vieweg J, Rosenthal FM, Bannerji R, et al.  Immunotherapy of prostate cancer in the Dunning rat model (Use of cytokine gene modified tumor vaccines). Cancer Res. 1994;54:1760–1765
  34. Zhang WW, Fang X, Mazur W, et al.  High-efficiency gene transfer and high level expression of wild-type p53 in human lung cancer cells mediated by recombinant adenovirus. Cancer Gene Ther. 1994;1:5–13
  35. Hall SJ, Mutchnik SE, Yang G, et al.  Cooperative therapeutic effects of androgen ablation and adenovirus-mediated herpes simplex virus-thymidine kinase gene and ganciclovir therapy in experimental prostate cancer. Cancer Gene Ther. 1999;6:54–63
  36. Timme TL, Hall SJ, Barrios R, et al.  Local inflammatory response and vector spread after direct intraprostatic injection of a recombinant adenovirus containing the herpes-simplex virus thymidine kinase gene and ganciclovir therapy in mice. Cancer Gene Ther. 1998;5:74–82
  37. Shalev M, Miles BJ, Thompson TC, et al.  Suicide gene therapy for prostate cancer using a replication-deficient adenovirus containing the herpesvirus thymidine kinase gene. World J Urol. 2000;18:125–129
  38. Kawashita Y, Ohtsuru A, Kaneda Y, et al.  Regression of hepatocellular carcinoma in vitro and in vivo by radiosensitizing suicide gene therapy under the inducible and spatial control of radiation. Hum Gene Ther. 1999;10:1509–1519
  39. Kim JH, Kim SH, Brown SL, et al.  Selective enhancement by an antiviral agent of the radiation-induced cell killing of human glioma cells transduced with HSV-tk gene. Cancer Res. 1994;54:6053–6056
  40. Nishihara E, Nagayama Y, Mawatari F, et al.  Retrovirus-mediated herpes simplex virus thymidine kinase gene transduction renders human thyroid carcinoma cell lines sensitive to ganciclovir and radiation in vitro and in vivo. Endocrinology. 1997;138(11):4577–4583
  41. Atkinson G, Hall S. Prodrug activation gene therapy and external beam irradiation in the treatment of prostate cancer. Urology. 1999;54:1098–1104
  42. Stevens CW, Zeng M, Cerniglia GJ. Ionizing radiation greatly improves gene transfer efficiency in mammalian cells. Hum Gene Ther. 1996;7:1727–1734
  43. Zeng M, Cerniglia GJ, Eck SL, et al.  High-efficiency stable gene transfer of adenovirus into mammalian cells using ionizing radiation. Hum Gene Ther. 1997;8:1025–1032
  44. Jain PT, Gerwirtz DA. Sustained enhancement of liposome-mediated gene delivery and gene expression in human breast tumor cells by ionizing radiation. Int J Radiat Oncol Biol Phys. 1999;75(2):217–223
  45. Simon WJ, Marshall FF. The future of gene therapy in the treatment of urologic malignancies. Urol Clin North Am. 1998;25:23–38
  46. Rodriguez LV, Terris MK. Risks and complications of transrectal ultrasound guided prostate needle biopsy (A prospective study and review of the literature). J Urol. 1998;160:2115–2120
  47. Ayala G, Wheeler TM, Shalev M, et al.  Cytopathic effect of in-situ gene therapy in prostate cancer. Hum Pathol. 2000;31:866–870

 This work was supported by a Specialized Program of Research Excellence (SPORE) grant (CA58204) from the National Cancer Institute, the Methodist Hospital Foundation, the General Clinical Research Center (GCRC), Advantagene, Glaxo-Welcome, and Schering Oncology.

PII: S0360-3016(01)01692-3

doi: 10.1016/S0360-3016(01)01692-3

International Journal of Radiation Oncology * Biology * Physics
Volume 51, Issue 3 , Pages 605-613 , 1 November 2001