Tasquinimod, an oral quinolone-3-carboxamide with anti-
tumor activity in preclinical models of
prostate cancer, has been tested in patients with minimally symptomatic
castration-resistant
prostate cancer (CRPC), showing promising inhibitory effects on the occurrence of
metastasis and delayed
disease progression. Although its mode of action is not fully understood,
tasquinimod presumably exerts its unique anti-
tumor action through inhibition of angiogenesis and
immunomodulation. In clinical studies,
tasquinimod demonstrated anti-
tumor activity in
prostate cancer in combination with a mild-to-moderate side effect profile. With single-agent
tasquinimod, dose-limiting toxicity was
amylase elevation without signs of
pancreatitis and
sinus tachycardia. The maximum tolerated dose in Phase I studies in patients with CRPC was once daily administration of 0.5-1-mg
tasquinimod orally. In a Phase II trial, significant clinical activity has been demonstrated in asymptomatic or minimally symptomatic,
chemotherapy-naive, metastatic CRPC (mCRPC) patients. Men were randomized to
tasquinimod or placebo in a 2:1 fashion; treatment with
tasquinimod resulted in significant improvement of median progression-free survival (7.6 vs 3.3 months with placebo; p = 0.0042). Based on these encouraging effects, a randomized, double-blind, placebo-controlled trial in men with minimally symptomatic mCRPC has been designed. This large Phase III trial, powered for a primary end point of progression-free survival, has now enrolled the target number of 1200 men. If the Phase II data are validated in the Phase III trial a new compound with a unique mode of action might become approved as a future
therapy for minimally symptomatic mCRPC patients.