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Prospective Evaluation of Zoledronic Acid in the Treatment of Bone Metastases from Differentiated Thyroid Carcinoma

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Abstract

Purpose

The objectives of this study were to prospectively delineate the efficacy and safety of zoledronic acid for treating bone metastases (BM) from differentiated thyroid carcinoma (DTC), and to evaluate the relationships between levels of bone metabolic markers and occurrence of skeletal-related events (SREs).

Methods

This was a prospective, single-arm, single-center study. Nineteen patients with BM from DTC were assigned to receive zoledronic acid therapy every 4–5 weeks. Imaging studies for sites of BM were conducted every 6 months, and levels of bone metabolic markers, including serum bone-specific alkaline phosphatase (BAP) and urinary N-telopeptide of type I collagen (NTx), were assessed every 3 months. To evaluate the efficacy of zoledronic acid use, data of SREs were compared with those of 16 historical controls.

Results

SREs developed in eight patients (42 %), but metastatic spinal cord compression (MSCC) appeared in only one patient. Pain scores were ameliorated in five patients, but aggravated in six patients. Ten patients had stable disease, six showed progressive disease, and none showed partial or complete response during the observation period. Decreases in levels of bone metabolic markers were observed in ten patients for BAP and 15 for NTx. However, no significant correlations were identified between changes in bone metabolic marker levels and development of SREs.

Conclusions

Zoledronic acid may offer a mainstay of multidisciplinary treatment for patients with BM for the purpose of reducing SREs. Levels of serum BAP and urinary NTx do not appear reliable as indicators of amelioration of BM symptoms.

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References

  1. Orita Y, Sugitani I, Matsuura M, Ushijima M, Tsukahara K, Fujimoto Y, et al. Prognostic factors and the therapeutic strategy for patients with bone metastasis from differentiated thyroid carcinoma. Surgery. 2010;147:424–31.

    Article  PubMed  Google Scholar 

  2. Sugitani I, Fujimoto Y, Yamamoto N. Papillary thyroid carcinoma with distant metastases: survival predictors and the importance of local control. Surgery. 2008;143:35–42.

    Article  PubMed  Google Scholar 

  3. Schlumberger M, Challeton C, De Vathaire F, et al. Radioactive iodine treatment and external radiotherapy for lung and bone metastases from thyroid carcinoma. J Nucl Med. 1996;37:598–605.

    CAS  PubMed  Google Scholar 

  4. Schlumberger M, Tubiana M, De Vathaire F, et al. Long-term results of treatment of 283 patients with lung and bone metastases from differentiated thyroid carcinoma. J Clin Endocrinol Metab. 1986;63:960–67.

    Article  CAS  PubMed  Google Scholar 

  5. Orita Y, Sugitani I, Toda K, Manabe J, Fujimoto Y. Zoledronic acid in the treatment of bone metastases from differentiated thyroid carcinoma. Thyroid. 2011;21:31–5.

    Article  CAS  PubMed  Google Scholar 

  6. Rosen HN, Moses AC, Garber J, Ross DS, Lee SL, Greenspan SL. Utility of biochemical markers of bone turnover in the follow-up of patients treated with bisphosphonates. Calcif Tissue Int. 1998;63:363–8.

    Article  CAS  PubMed  Google Scholar 

  7. Hernandez RK, Quigley J, Pirolli M, Quach D, Chen KS, Arellano J, et al. Patients with bone metastases from solid tumors initiating treatment with a bone-targeted agent in 2011: a descriptive analysis using oncology clinic data in the US. Support Care Cancer. 2014;22:2697–705.

    Article  PubMed  Google Scholar 

  8. Rosen LS, Gordon D, Kaminski M, et al. Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer. 2003;98:1735–44.

    Article  CAS  PubMed  Google Scholar 

  9. Rosen LS, Gordon D, Tchekmedyian NS, et al. Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors. A randomized, phase III, double-blind, placebo-controlled trial. Cancer. 2004;100:2613–21.

    Article  CAS  PubMed  Google Scholar 

  10. Ravn P, Clemmesen B, Christiansen C. Biochemical markers can predict the response in bone mass during alendronate treatment in early postmenopausal woman. Bone. 1999;24:237–44.

    Article  CAS  PubMed  Google Scholar 

  11. Chong S, Shin SH, Yoo H, Lee SH, Kim KJ, Jahng TA, et al. Single-stage posterior decompression and stabilization for metastasis of the thoracic spine: prognostic factors for functional outcome and patients’ survival. Spine J. 2012;12:1083–92.

    Article  PubMed  Google Scholar 

  12. Cartsos VM, Zhu S, Zavras AI. Bisphosphonate use and the risk of adverse jaw outcomes. A medical claims study of 714,217 people. J Am Dent Assoc. 2008;139:23–30.

    Article  PubMed  Google Scholar 

  13. Durie BG, Katz M, Crowley J. Osteonecrosis of the jaw and bisphosphonates. N Engl J Med. 2005;353:99–102.

    Article  CAS  PubMed  Google Scholar 

  14. Maisano R, Pergolizzi S, Cascinu S. Novel therapeutic approaches to cancer patients with bone metastasis. Crit Rev Oncol Hematol. 2001;40:239–50.

    Article  CAS  PubMed  Google Scholar 

  15. Vinholes JJ, Purohit OP, Abbey ME, Eastell R, Coleman RE. Relationships between biochemical and symptomatic response in a double-blind randomized trial of pamidronate for metastatic bone disease. Ann Oncol. 1997;8:1243–50.

    Article  CAS  PubMed  Google Scholar 

  16. Radziwill AJ, Thurlimann B, Jungi WF. Improvement of palliation in patients with osteolytic bone disease and unsatisfactory pain control after pretreatment with disodium pamidronate: an intra-patient dose escalation study. Onkologie. 1993;16:174–7.

    Article  Google Scholar 

  17. Hitron A, Adams V. The pharmacological management of skeletal-related events from metastatic tumors. Orthopedics. 2009;32:188–92.

    Article  PubMed  Google Scholar 

  18. Storto G, Klain M, Paone G, et al. Combined therapy of Sr-89 and zoledronic acid in patients with painful bone metastases. Bone. 2006;39:35–41.

    Article  CAS  PubMed  Google Scholar 

  19. McFarland DC, Misiukiewicz KJ. Sorafenib in radioactive iodine-refractory well-differentiated metastatic thyroid cancer. Onco Targets Ther. 2014;15:1291–9.

    Article  Google Scholar 

  20. Piovesan A, Berruti A, Torta M, et al. Comparison of assay of total and bone-specific alkaline phosphatase in the assessment of osteoblast activity in patients with metastatic bone disease. Calcif Tissue Int. 1997;61:362–9.

    Article  CAS  PubMed  Google Scholar 

  21. Randall AG, Kent GN, Garcia-Webb P, et al. Comparison of biochemical markers of bone turnover in paget disease treated with pamidronate and proposed model for the relationships between measurements of the different forms of pyridinoline cross-links. J Bone Miner Res. 1996;11:1176–84.

    Article  CAS  PubMed  Google Scholar 

  22. Costa L, Demers LM, Gouveia-Oliveira A, Schaller J, Costa EB, de Moura MC, et al. Prospective evaluation of the peptide-bound collagen type I cross-links N-telopeptide and C-telopeptide in predicting bone metastases status. J Clin Oncol. 2002;20:850–6.

    Article  CAS  PubMed  Google Scholar 

  23. Kamiya N, Suzuki H, Endo T, et al. Clinical usefulness of bone markers in prostate cancer with bone metastasis. Int J Urol. 2012;19:968–79.

    Article  CAS  PubMed  Google Scholar 

  24. Rajpar S, Massard C, Laplanche A, et al. Urinary N-telopeptide (uNTx) is an independent prognostic factor for overall survival in patients with bone metastases from castration-resistant prostate cancer. Ann Oncol. 2010;21:1864–9.

    Article  CAS  PubMed  Google Scholar 

  25. Lipton A, Cook RJ, Major P, Smith MR, Coleman RE. Zoledronic acid and survival in breast cancer patients with bone metastases and elevated markers of osteoclast activity. Oncology. 2007;12:1035–43.

    Article  CAS  Google Scholar 

  26. Clezardin P. The antitumor potential of bisphosphonates. Semin Oncol. 2002;29:33–42.

    CAS  PubMed  Google Scholar 

  27. Vitale G, Fonderico F, Martignetti A, et al. Pamidronate improves the quality of life and induces clinical remission of bone metastases in patients with thyroid cancer. Br J Cancer. 2001;84:1586–90.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Zhao H, Han KL, Wang ZY, et al. Value of C-telopeptide-cross-linked type I collagen, osteocalcin, bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide in the diagnosis and prognosis of bone metastasis in patients with malignant tumors. Med Sci Monit. 2011;17:CR626–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Disclosure

Yorihisa Orita, Iwao Sugitani, Soshi Takao, Kazuhisa Toda, Jun Manabe, and Satoshi Miyata have no conflicts of interest, potential conflicts, or financial relationships to declare.

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Authors and Affiliations

  1. Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan

    Yorihisa Orita MD, PhD

  2. Division of Endocrine Surgery, Department of Surgery, Nippon Medical School, Tokyo, Japan

    Iwao Sugitani MD, PhD

  3. Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan

    Soshi Takao MD, PhD

  4. Division of Head and Neck, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan

    Kazuhisa Toda MD

  5. Division of Orthopedics, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan

    Jun Manabe MD, PhD

  6. Division of Statistics, Genome Center of the Japanese Foundation for Cancer Research, Tokyo, Japan

    Satoshi Miyata MD, PhD

Authors
  1. Yorihisa Orita MD, PhD
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  2. Iwao Sugitani MD, PhD
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  3. Soshi Takao MD, PhD
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  4. Kazuhisa Toda MD
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  5. Jun Manabe MD, PhD
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  6. Satoshi Miyata MD, PhD
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Corresponding author

Correspondence to Yorihisa Orita MD, PhD.

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Orita, Y., Sugitani, I., Takao, S. et al. Prospective Evaluation of Zoledronic Acid in the Treatment of Bone Metastases from Differentiated Thyroid Carcinoma. Ann Surg Oncol 22, 4008–4013 (2015). https://doi.org/10.1245/s10434-015-4497-0

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  • DOI: https://doi.org/10.1245/s10434-015-4497-0

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