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A Mathematical Model of Intermittent Androgen Suppression for Prostate Cancer

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Abstract

For several decades, androgen suppression has been the principal modality for treatment of advanced prostate cancer. Although the androgen deprivation is initially effective, most patients experience a relapse within several years due to the proliferation of so-called androgen-independent tumor cells. Bruchovsky et al. suggested in animal models that intermittent androgen suppression (IAS) can prolong the time to relapse when compared with continuous androgen suppression (CAS). Therefore, IAS has been expected to enhance clinical efficacy in conjunction with reduction in adverse effects and improvement in quality of life of patients during off-treatment periods. This paper presents a mathematical model that describes the growth of a prostate tumor under IAS therapy based on monitoring of the serum prostate-specific antigen (PSA). By treating the cancer tumor as a mixed assembly of androgen-dependent and androgen-independent cells, we investigate the difference between CAS and IAS with respect to factors affecting an androgen-independent relapse. Numerical and bifurcation analyses show how the tumor growth and the relapse time are influenced by the net growth rate of the androgen-independent cells, a protocol of the IAS therapy, and the mutation rate from androgen-dependent cells to androgen-independent ones.

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Abbreviations

AD::

androgen-dependent;

ADT::

androgen deprivation therapy;

AI::

androgen-independent;

CAS::

continuous androgen suppression;

IAS::

intermittent androgen suppression;

LHRH::

luteinizing hormone releasing hormone;

MAB::

maximal androgen blockade;

PSA::

prostate-specific antigen.

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Authors and Affiliations

  1. ERATO Aihara Complexity Modelling Project, JST, Tokyo, 153-8505, Japan

    Aiko Miyamura Ideta & Kazuyuki Aihara

  2. Institute of Industrial Science, University of Tokyo, Tokyo, 153-8505, Japan

    Gouhei Tanaka & Kazuyuki Aihara

  3. Department of Urology, University of Tokyo, Tokyo, 113-8655, Japan

    Takumi Takeuchi

Authors
  1. Aiko Miyamura Ideta
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  2. Gouhei Tanaka
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  3. Takumi Takeuchi
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  4. Kazuyuki Aihara
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Correspondence to Kazuyuki Aihara.

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Ideta, A.M., Tanaka, G., Takeuchi, T. et al. A Mathematical Model of Intermittent Androgen Suppression for Prostate Cancer. J Nonlinear Sci 18, 593 (2008). https://doi.org/10.1007/s00332-008-9031-0

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