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Impact of everolimus blood concentration on its anti-cancer activity in patients with metastatic renal cell carcinoma

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Abstract

Purpose

Everolimus has demonstrated its efficacy in metastatic renal cell carcinoma (mRCC). Preliminary studies have shown high variability of everolimus blood concentrations (EBC). In other settings, its activity was correlated with EBC. We therefore decided to monitor EBC in patients treated with mRCC to assess its influence on oncologic outcomes.

Patients and methods

Our study analyzed first 3 months’ trough EBC levels in 42 patients treated in 4 French oncologic centers between March 2010 and August 2013. Patients presented a histologically confirmed diagnosis of mRCC and have failed prior anti-angiogenic (AA) therapies.

Results

Median follow-up was 25.9 months. A total of 113 EBC were analyzed. The median trough concentration was 14.1 μg/L (range 2.6–91.5). Fourteen patients (67 %) versus 8 (38 %) patients with median EBC above or below 14.1 μg/L were free from progression at 6 months (p = 0.06). Median progression-free survival was 13.3 versus 3.9 months (HR 0.66 95 % CI 0.33–1.31; p = 0.23), and the median overall survival was 26.2 versus 9.9 months (HR 0.62 95 % CI 0.28–1.37; p = 0.24), for patients above or below the median value of trough concentrations, respectively.

Conclusion

Impact of drug exposure for AA tyrosine kinase inhibitors activity has been demonstrated in mRCC setting. Interpatients EBC variability was confirmed in the present study, and the results suggest a relationship between initial EBC within the first 3 months and the drug activity. It underlines the need to prospectively include EBC monitoring in future clinical trials to determine the need of its implementation in routine use.

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Acknowledgments

We would like to thank all the medical teams of our oncology departments, all the staff of pharmacology unit and the nurses that render possible the publication of this report. Antoine Thiery-Vuillemin and Bernard Royer have been paid directly honorarias (reasonable payments for specific speeches, seminar presentations) from 2 years prior the present work by Novartis.

Conflict of interest

The authors do not have any conflict of interest to disclose relevant for this article. No Research Funding, No stock ownership.

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Authors and Affiliations

  1. Department of Oncology, CHU Besançon, 25030, Besançon Cedex, France

    A. Thiery-Vuillemin, G. Mouillet, T. Nguyen Tan Hon, P. Montcuquet, T. Maurina, H. Almotlak, U. Stein & X. Pivot

  2. UMR1098, INSERM, 25020, Besançon Cedex, France

    A. Thiery-Vuillemin, X. Pivot & B. Royer

  3. UMR1098, SFR IBCT, University of Franche-Comté, 25020, Besançon Cedex, France

    A. Thiery-Vuillemin, X. Pivot & B. Royer

  4. Methodology and Quality of Life in Oncology Unit (EA 3181), CHU Besançon, 25030, Besançon Cedex, France

    G. Mouillet & A. Foubert

  5. Department of Oncology, CH Dôle, 39108, Dôle, France

    G. Mouillet

  6. Department of Oncology, Polyclinique de Franche-Comté, 25000, Besançon Cedex, France

    T. Nguyen Tan Hon

  7. Department of Oncology, CHBM, 25209, Montbeliard, France

    T. Maurina

  8. Department of Oncology, CH Vesoul, 70000, Vesoul, France

    P. Montcuquet & U. Stein

  9. Department of Oncology, CH Lons-le-Saunier, 39000, Lons-le-Saunier, France

    H. Almotlak

  10. Department of Pharmacology, CHU Besançon, 25030, Besançon Cedex, France

    D. Montange & B. Royer

  11. Department of Pharmacy, CHU Besançon, 25030, Besançon cedex, France

    V. Nerich

  12. Medical Oncology, CHU Jean minjoz, Boulevard Flemming, 25000, Besançon Cedex, France

    A. Thiery-Vuillemin

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  1. A. Thiery-Vuillemin
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  2. G. Mouillet
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  8. D. Montange
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Corresponding author

Correspondence to A. Thiery-Vuillemin.

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Thiery-Vuillemin, A., Mouillet, G., Nguyen Tan Hon, T. et al. Impact of everolimus blood concentration on its anti-cancer activity in patients with metastatic renal cell carcinoma. Cancer Chemother Pharmacol 73, 999–1007 (2014). https://doi.org/10.1007/s00280-014-2435-7

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  • DOI: https://doi.org/10.1007/s00280-014-2435-7

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