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Local and systemic diffusion of antineoplastic drugs following vertebroplasty using acrylic cement mixed with cisplatin or methotrexate: experimental study in pigs

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Abstract

Purpose

To determine the efficacy of cisplatin- or methotrexate-containing acrylic cement for local and systemic antineoplastic drug diffusion. Among the uses of acrylic cement or Polymethylmethacrylate (PMMA), there is the possibility to employ it as vehicle for drug diffusion. This capability is of interest in the treatment of pathological fractures: The curative effects of the cement (cytotoxicity of the monomer and increased temperature) are added to the antineoplastic effect of the drugs.

Methods

In the experimental study, two groups of ten pigs underwent vertebroplasty using cement mixed with 500 mg of powder cisplatin or 1000 mg of powder methotrexate. Vertebroplasty was performed in two non-consecutive lumbar vertebrae with bipedicular cement injection. Transpedicular bone biopsy was performed weekly to measure levels of antineoplastic agent in bone tissue and blood plasma. Cisplatin was studied by atomic absorption spectrometry and methotrexate by fluorescence polarization immunoassay. Renal and hepatic function and blood analysis were performed weekly.

Results

Cisplatin and methotrexate levels were found in bone tissue at more than 5 weeks following surgery. The cisplatin peak occurred at week 3 (mean 1269 μg/g bone) and the methotrexate peak at week 1 (mean 862.76 μg/g bone). Plasma drug levels were found 72 h after surgery, with a peak at 24 h for cisplatin (mean 0.23 μmol/L) and at 30 min for methotrexate (mean 0.92 μmol/L). None of the animals died during the study. Animals with intracanal cement leaks showed no neurological involvement. Renal, hepatic and hemogram studies remained within normal limits.

Conclusions

There is local diffusion of antineoplastic agents from the cement to bone and plasma. We found methotrexate and cisplatin levels in bone at up to 5 weeks, comparable to previous in vitro reports. At the doses administered, there were no cases of myelosuppression, hepatotoxicity, or nephrotoxicity.

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Acknowledgements

For this study, we obtained two Grands: Sociedad Española de Cirugía Ortopédica y Traumatología (SECOT) Beca proyecto de inicio a la investigación 2013. Spanish Spine Society (GEER) Beca Investigación GEER 2012.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Clínica Universidad de Navarra, Pio XII 36, 31008, Pamplona, Spain

    Rafael Llombart-Blanco, Carlos Villas & Matías Alfonso

  2. Department of Orthopaedic Surgery, German Clinic of Santiago, Universidad del Desarrollo, Av Maquehue Norte 1410, Vitacura, Santiago, Chile

    Álvaro Silva

  3. Department of Hospital Pharmacy, Clínica Universidad de Navarra, Pio XII 36, 31008, Pamplona, Spain

    Azucena Aldaz

  4. Department of Chemistry and Edafology, Universidad de Navarra, Edificio de investigación, C/Irunlrrea 1, 31008, Pamplona, Spain

    Iñigo Navarro

  5. Instituto Valenciano de Patologia, Universidad Catolica de Valencia, C/Quevedo 2, 46001, Valencia, Spain

    Jeronimo Forteza

  6. Department of Oncology, Clínica Universidad de Navarra, Pio XII 36, 31008, Pamplona, Spain

    Salvador Martin Algarra

Authors
  1. Rafael Llombart-Blanco
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  2. Carlos Villas
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  7. Salvador Martin Algarra
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  8. Matías Alfonso
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Corresponding author

Correspondence to Rafael Llombart-Blanco.

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Llombart-Blanco, R., Villas, C., Silva, Á. et al. Local and systemic diffusion of antineoplastic drugs following vertebroplasty using acrylic cement mixed with cisplatin or methotrexate: experimental study in pigs. Eur Spine J 26, 3216–3224 (2017). https://doi.org/10.1007/s00586-017-4980-3

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  • DOI: https://doi.org/10.1007/s00586-017-4980-3

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