Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Clinical Research

Long-term follow-up of prostate cancer patients treated with vaccine and definitive radiation therapy

Prostate Cancer and Prostatic Diseases volume 15, pages 289–295 (2012)Cite this article

Subjects

Abstract

Background:

Vaccine therapy in combination with radiation therapy may improve distant and/or local control in prostate cancer. We present long-term follow-up data on the secondary and exploratory endpoints of safety and biochemical failure, respectively, from patients with clinically localized prostate cancer treated definitively with a poxviral vector-based therapeutic vaccine combined with external beam radiation therapy (EBRT).

Methods:

Thirty-six prostate cancer patients received definitive EBRT plus vaccine. A total of 18 patients were treated with adjuvant standard-dose interleukin-2 (S-IL-2) (4 MIU m–2) and 18 were treated with very low-dose IL-2 (M-IL-2) (0.6 MIU m–2). Seven patients were treated with EBRT alone. Twenty-six patients treated with EBRT plus vaccine returned for follow-up, and we reviewed the most recent labs and clinical notes of the remaining patients.

Results:

Median follow-up for the S-IL-2, M-IL-2 and EBRT-alone groups was 98, 76 and 79 months, respectively. Actuarial 5-year PSA failure-free probability was 78%, 82% and 86% (P=0.58 overall), respectively. There were no significant differences between the actuarial overall survival and the prostate cancer-specific survival between the two vaccine arms. Of the 26 patients who returned for follow-up, Radiation Therapy Oncology Group grade ⩾2 genitourinary (GU) and gastrointestinal (GI) toxicity was seen in 19% and 8%, respectively, with no difference between the arms (P=1.00 and P=0.48 for grade ⩾2 GU and GI toxicity, respectively). In all, 12 patients were evaluated for PSA-specific immune responses, and 1 demonstrated a response 66 months post-enrollment.

Conclusions:

We demonstrate that vaccine combined with EBRT does not appear to have significant differences with regard to PSA control or late-term toxicity compared with standard treatment. We also found limited evidence of long-term immune response following vaccine therapy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Hanks GE, Pajak TF, Porter A, Grignon D, Brereton H, Venkatesan V et al. Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: the radiation therapy oncology group protocol 92–02. J Clin Oncol 2003; 21: 3972–3978.

    Article  CAS  Google Scholar 

  2. Dearnaley DP, Sydes MR, Graham JD, Aird EG, Bottomley D, Cowan RA et al. Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial. Lancet Oncol 2007; 8: 475–487.

    Article  Google Scholar 

  3. Zietman AL, DeSilvio ML, Slater JD, Rossi Jr CJ, Miller DW, Adams JA et al. Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial. JAMA 2005; 294: 1233–1239.

    Article  CAS  Google Scholar 

  4. Allen GW, Howard AR, Jarrard DF, Ritter MA . Management of prostate cancer recurrences after radiation therapy-brachytherapy as a salvage option. Cancer 2007; 110: 1405–1416.

    Article  Google Scholar 

  5. Khuntia D, Reddy CA, Mahadevan A, Klein EA, Kupelian PA . Recurrence-free survival rates after external-beam radiotherapy for patients with clinical T1-T3 prostate carcinoma in the prostate-specific antigen era: what should we expect? Cancer 2004; 100: 1283–1292.

    Article  Google Scholar 

  6. Kuban DA, Thames HD, Levy LB, Horwitz EM, Kupelian PA, Martinez AA et al. Long-term multi-institutional analysis of stage T1-T2 prostate cancer treated with radiotherapy in the PSA era. Int J Radiat Oncol Biol Phys 2003; 57: 915–928.

    Article  Google Scholar 

  7. Nguyen PL, D’Amico AV, Lee AK, Suh WW . Patient selection, cancer control, and complications after salvage local therapy for postradiation prostate-specific antigen failure: a systematic review of the literature. Cancer 2007; 110: 1417–1428.

    Article  Google Scholar 

  8. Gulley JL, Arlen PM, Bastian A, Morin S, Marte J, Beetham P et al. Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer. Clin Cancer Res 2005; 11: 3353–3362.

    Article  CAS  Google Scholar 

  9. Lechleider RJ, Arlen PM, Tsang KY, Steinberg SM, Yokokawa J, Cereda V et al. Safety and immunologic response of a viral vaccine to prostate-specific antigen in combination with radiation therapy when metronomic-dose interleukin 2 is used as an adjuvant. Clin Cancer Res 2008; 14: 5284–5291.

    Article  CAS  Google Scholar 

  10. Arlen PM, Gulley JL, Parker C, Skarupa L, Pazdur M, Panicali D et al. A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer. Clin Cancer Res 2006; 12: 1260–1269.

    Article  CAS  Google Scholar 

  11. Britten CM, Meyer RG, Kreer T, Drexler I, Wolfel T, Herr W . The use of HLA-A*0201-transfected K562 as standard antigen-presenting cells for CD8(+) T lymphocytes in IFN-gamma ELISPOT assays. J Immunol Methods 2002; 259: 95–110.

    Article  CAS  Google Scholar 

  12. Miller DC, Sanda MG, Dunn RL, Montie JE, Pimentel H, Sandler HM et al. Long-term outcomes among localized prostate cancer survivors: health-related quality-of-life changes after radical prostatectomy, external radiation, and brachytherapy. J Clin Oncol 2005; 23: 2772–2780.

    Article  Google Scholar 

  13. Rosenthal SA, Bae K, Pienta KJ, Sobczak ML, Asbell SO, Rajan R et al. Phase III multi-institutional trial of adjuvant chemotherapy with paclitaxel, estramustine, and oral etoposide combined with long-term androgen suppression therapy and radiotherapy versus long-term androgen suppression plus radiotherapy alone for high-risk prostate cancer: preliminary toxicity analysis of RTOG 99–02. Int J Radiat Oncol Biol Phys 2009; 73: 672–678.

    Article  CAS  Google Scholar 

  14. Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004; 351: 1502–1512.

    Article  CAS  Google Scholar 

  15. Kantoff PW, Schuetz TJ, Blumenstein BA, Glode LM, Bilhartz DL, Wyand M et al. Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol 2010; 28: 1099–1105.

    Article  CAS  Google Scholar 

  16. Gulley JL, Arlen PM, Madan RA, Tsang KY, Pazdur MP, Skarupa L et al. Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer. Cancer Immunol Immunother 2010; 59: 663–674.

    Article  CAS  Google Scholar 

  17. Bavarian Nordic Receives Special Protocol Assessment Agreement from the FDA for Phase 3 Trial of PROSTVAC®, 08 December 2010. [cited October 2011]; Available from: http://www.bavarian-nordic.com/investor/announcements/2010-40.aspx; 2011.

  18. D’Amico AV, Chen MH, Renshaw AA, Loffredo M, Kantoff PW . Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial. JAMA 2008; 299: 289–295.

    Article  Google Scholar 

  19. Lawton CA, Bae K, Pilepich M, Hanks G, Shipley W . Long-term treatment sequelae after external beam irradiation with or without hormonal manipulation for adenocarcinoma of the prostate: analysis of radiation therapy oncology group studies 85–31, 86–10, and 92–02. Int J Radiat Oncol Biol Phys 2008; 70: 437–441.

    Article  CAS  Google Scholar 

  20. Garnett CT, Greiner JW, Tsang KY, Kudo-Saito C, Grosenbach DW, Chakraborty M et al. TRICOM vector based cancer vaccines. Curr Pharm Des 2006; 12: 351–361.

    Article  CAS  Google Scholar 

  21. Grosenbach DW, Barrientos JC, Schlom J, Hodge JW . Synergy of vaccine strategies to amplify antigen-specific immune responses and antitumor effects. Cancer Res 2001; 61: 4497–4505.

    CAS  PubMed  Google Scholar 

  22. Hodge JW, Sabzevari H, Yafal AG, Gritz L, Lorenz MG, Schlom J . A triad of costimulatory molecules synergize to amplify T-cell activation. Cancer Res 1999; 59: 5800–5807.

    CAS  PubMed  Google Scholar 

  23. Yang S, Hodge JW, Grosenbach DW, Schlom J . Vaccines with enhanced costimulation maintain high avidity memory CTL. J Immunol 2005; 175: 3715–3723.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, University of California at Los Angeles, Los Angeles, CA, USA

    M Kamrava

  2. Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    A H Kesarwala, E Lita & A Kaushal

  3. Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    R A Madan, K-Y Tsang, D J Poole, T Ferrara, J Schlom & J L Gulley

  4. Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    R A Madan, W Dahut & J L Gulley

  5. Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    S M Steinberg

Authors
  1. M Kamrava
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A H Kesarwala
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R A Madan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E Lita
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Kaushal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K-Y Tsang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. D J Poole
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S M Steinberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. T Ferrara
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. W Dahut
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. J Schlom
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. J L Gulley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J L Gulley.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kamrava, M., Kesarwala, A., Madan, R. et al. Long-term follow-up of prostate cancer patients treated with vaccine and definitive radiation therapy. Prostate Cancer Prostatic Dis 15, 289–295 (2012). https://doi.org/10.1038/pcan.2012.7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/pcan.2012.7

Keywords

This article is cited by

Search

Advanced search

Quick links