A Mathematical Model of Intermittent Androgen Suppression Remedy for Prostate Cancer

Androgen suppression has been the principal modality for treatment of advanced prostate cancer for several decades. Although the tumor response rate to androgen deprivation is initially high, almost all patients relapse within several years due to proliferation of androgenindependent tumor cells. Since Bruchovsky et al. suggested in animal models that intermittent androgen suppression can prolong the time to relapse compared with continuous androgen suppression, intermittent medication has been expected to enhance clinical efficacy in conjunction with reduction of adverse effects and improvement of patient’s quality of life during off-treatment periods. This paper presents a mathematical model that describes growth of prostate tumor under intermittent androgen suppression therapy based on monitoring of serum prostate-specific antigen. Treating the cancerous tumor as an assembly of androgen-dependent and androgen-independent cells, we investigate the difference between continuous and intermittent androgen suppressions in the effects on androgen-independent relapse. Numerical and bifurcation analyses show how the tumor growth is influenced by the proliferation rate of androgen-independent cells, metastatic sites, and the prostate-specific antigen levels to stop and reinstitute the androgen suppression.