Skip to main content

Advertisement

SpringerLink
Log in

Possible anti-tumor activity of initial treatment with zoledronic acid with hormonal therapy for bone-metastatic prostate cancer in multicenter clinical trial

  • Original Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

To ascertain the anti-tumor effect of zoledronic acid (ZOL) treatment on clinical outcomes in patients with bone metastatic prostate cancer, we examined the effect of ZOL started simultaneously with hormonal therapy as initial treatment in these patients.

Methods

Forty-seven patients with bone-metastatic prostate cancer who received a luteinizing hormone releasing-hormone (LHRH) analogue and an anti-androgen [maximal androgen blockade (MAB)] were assigned to receive ZOL (4 mg intravenous administration every month for 2 years). The time to progression (TTP) of the prostate-specific antigen (PSA), the overall survival (OS), and the rate of PSA decrease in patients with MAB and ZOL treatment (ZOL group) were compared with these parameters in patients who received only MAB at one institute as a control group (non-ZOL group).

Results

Although the nadir PSA level and the rate of PSA normalization showed no significant differences between the ZOL and non-ZOL groups, the time to nadir PSA in the ZOL group was significantly shorter than that in the non-ZOL group (P < 0.05, Mann–Whitney U-test). There was a significant difference in TTP (P = 0.017, log-rank test) between the ZOL and non-ZOL groups, and statistically significant differences in TTP and OS between the ZOL and non-ZOL groups (P = 0.044 and 0.035, log-rank test) were recognized particularly in patients with advanced disease (extension of disease, grade 3 and 4).

Conclusions

Simultaneous administration of ZOL and MAB as initial treatment delayed TTP in bone-metastatic prostate cancer patients. Initial treatment with ZOL has the possibility of anti-tumor activity to delay disease progression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Cooperberg MR, Hinotsu S, Namiki M et al (2009) Assessment among prostate cancer patients receiving primary androgen deprivation therapy. J Clin Oncol 27:4306–4313

    Article  PubMed  Google Scholar 

  2. Huggins C, Hodges CV (1972) Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. CA Cancer J Clin 22:232–240

    Article  PubMed  CAS  Google Scholar 

  3. Coleman RE (2001) Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev 27:165–176

    Article  PubMed  CAS  Google Scholar 

  4. Brown JE, Cook RJ, Major P et al (2005) Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors. J Natl Cancer Inst 97:59–69

    Article  PubMed  CAS  Google Scholar 

  5. Demers LM (2003) Bone markers in the management of patients with skeletal metastases. Cancer 97(3 Suppl):874–879

    Article  PubMed  Google Scholar 

  6. Percival RC, Urwin GH, Harris S et al (1987) Biochemical and histological evidence that carcinoma of the prostate is associated with increased bone resorption. Eur J Surg Oncol 13:41–49

    PubMed  CAS  Google Scholar 

  7. Saad F, Gleason DM, Murray R et al (2004) Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 96:879–882

    Article  PubMed  CAS  Google Scholar 

  8. Aapro M, Abrahamsson PA, Body JJ et al (2008) Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel. Ann Oncol 19:420–432

    Article  PubMed  CAS  Google Scholar 

  9. Gnant M, Mlineritsch B, Schippinger W et al (2009) Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med 360:679–691

    Article  PubMed  CAS  Google Scholar 

  10. Eidtmann H, de Boer R, Bundred N et al (2010) Efficacy of zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36-month results of the ZO-FAST Study. Ann Oncol 21:2188–2194

    Article  PubMed  CAS  Google Scholar 

  11. Soloway MS, Hardeman SW, Hickey D et al (1988) Stratification of patients with metastatic prostate cancer based on extent of disease on initial bone scan. Cancer 61:195–202

    Article  PubMed  CAS  Google Scholar 

  12. DePuy V, Anstrom KJ, Castel LD et al (2007) Effects of skeletal morbidities on longitudinal patient-reported outcomes and survival in patients with metastatic prostate cancer. Support Care Cancer 15:869–876

    Article  PubMed  Google Scholar 

  13. Yigitbasi O, Ozturk U, Goktug HN et al (2011) Prognostic factors in metastatic prostate cancer. Urol Oncol 29:162–165

    Article  PubMed  Google Scholar 

  14. Saad F, Gleason DM, Murray R et al (2002) A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 94:1458–1468

    Article  PubMed  CAS  Google Scholar 

  15. Velde NV, Wu EQ, Guo A et al (2011) The benefits of timely intervention with zoledronic acid in patients with metastatic prostate cancer to bones: a retrospective study of the US Veterans Affairs population. Prostate Cancer Prostatic Dis 14:79–84

    Article  PubMed  CAS  Google Scholar 

  16. Winter MC, Holen I, Coleman RE (2008) Exploring the anti-tumour activity of bisphosphonates in early breast cancer. Cancer Treat Rev 34:453–475

    Article  PubMed  CAS  Google Scholar 

  17. Vincenzi B, Santini D, Dicuonzo G et al (2005) Zoledronic acid-related angiogenesis modifications and survival in advanced breast cancer patients. J Interferon Cytokine Res 25:144–151

    Article  PubMed  CAS  Google Scholar 

  18. Mottet N, Bellmunt J, Bolla M et al (2011) EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol 59:572–583

    Article  PubMed  Google Scholar 

  19. Saad F, Eastham J (2010) Zoledronic acid improves clinical outcomes when administered before onset of bone pain in patients with prostate cancer. Urology 76:1175–1181

    Article  PubMed  Google Scholar 

  20. Bundred NJ, Campbell ID, Davidson N et al (2008) Effective inhibition of aromatase inhibitor-associated bone loss by zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: ZO-FAST Study results. Cancer 112:1001–1010

    Article  PubMed  CAS  Google Scholar 

  21. Coleman R, Cook R, Hirsh V et al (2011) Zoledronic acid use in cancer patients: more than just supportive care? Cancer 117:11–23

    Article  PubMed  CAS  Google Scholar 

  22. Santini D, Vincenzi B, Galluzzo S et al (2007) Repeated intermittent low-dose therapy with zoledronic acid induces an early, sustained, and long-lasting decrease of peripheral vascular endothelial growth factor levels in cancer patients. Clin Cancer Res 13(15 Pt 1):4482–4486

    Article  PubMed  CAS  Google Scholar 

  23. Melisi D, Caputo R, Damiano V et al (2005) Zoledronic acid cooperates with a cyclooxygenase-2 inhibitor and gefitinib in inhibiting breast and prostate cancer. Endocr Relat Cancer 12:1051–1058

    Article  PubMed  CAS  Google Scholar 

  24. Neville-Webbe HL, Rostami-Hodjegan A, Evans CA et al (2005) Sequence- and schedule-dependent enhancement of zoledronic acid induced apoptosis by doxorubicin in breast and prostate cancer cells. Int J Cancer 113:364–371

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

All authors declare they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan

    Hiroji Uemura & Yoshinobu Kubota

  2. Department of Urology, Yokohama Minami Kyousai Hospital, 1-21-1 Mutsuura-higashi, Kanazawa-ku, Yokohama, 236-0037, Japan

    Masahiro Yanagisawa & Ichirou Ikeda

  3. Department of Urology, Chigasaki City Hospital, 5-15-1 Motomura, Chigasaki, 253-0042, Japan

    Kiyoshi Fujinami

  4. Department of Urology, Yokohama Minato Red Cross Hospital, 3-12-1 Shin-Yamashita, Naka-ku, Yokohama, 231-8682, Japan

    Akira Iwasaki

  5. Department of Urology, Yokosuka Kyousai Hospital, 1-16 Yonegahama-dori, Yokosuka, 238-8558, Japan

    Sumio Noguchi

  6. Department of Urology, Yokohama City University Center Hospital, 4-57 Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan

    Kazumi Noguchi

Authors
  1. Hiroji Uemura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masahiro Yanagisawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ichirou Ikeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kiyoshi Fujinami
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Akira Iwasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sumio Noguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kazumi Noguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yoshinobu Kubota
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

Yokohama Bone Metastasis Study Group

Corresponding author

Correspondence to Hiroji Uemura.

Additional information

Members of the Yokohama Bone Metastasis Study Group are listed in the Appendix.

Appendix: Yokohama Bone Metastasis Study Group

Appendix: Yokohama Bone Metastasis Study Group

Yokohama City University Hospital (Prof. Y. Kubota), Yokohama City University Center Hospital (Prof. K. Noguchi), Yokosuka Kyousai Hospital (Dr. S. Noguchi), Yokohama Minato Red Cross Hospital (Dr. A. Iwasaki), Chigasaki City Hospital (Dr. K. Fujinami), Yokohama City Hospital (Dr. M. Moriyama), Kokusai Shinzen Hospital (Dr. T. Murayama), Kawasaki City Ida Hospital (Dr. K. Chiba), and Toshiba Rinkan Hospital (Dr. H. Kanno).

About this article

Cite this article

Uemura, H., Yanagisawa, M., Ikeda, I. et al. Possible anti-tumor activity of initial treatment with zoledronic acid with hormonal therapy for bone-metastatic prostate cancer in multicenter clinical trial. Int J Clin Oncol 18, 472–477 (2013). https://doi.org/10.1007/s10147-012-0406-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-012-0406-8

Keywords

Search

Navigation