Prevention and treatment of metastatic disease in thrombocytotic cancer patients
INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
International Publication Number
WO 2016/102952 Al
[001] The present invention relates to the use of the anti-megakaryocytic agent anagrelide or a therapeutically active metabolite thereof, in the prevention and/or treatment of metastatic disease in cancer patients displaying paraneoplastic thrombocytosis. In particular the invention relates to reducing the formation and progression of potentially fatal bone, lung and other metastases most evident in such patients.
[002] The present invention also relates to the use of the anti-megakaryocytic agent anagrelide or a therapeutically active metabolite thereof, for enhancing the efficacy of conventional cancer chemotherapeutic drugs in thrombocytotic cancer patients.
[003] The drug may be formulated in an appropriate side-effect modulating (SEM)/cardiacsparing formulation, which minimises the PDEIII inhibitory actions and thereby cardiostimulant activity of the drug. Suitable formulations include those previously established to reduce or avoid first pass metabolism and thus, in this case, the generation of anagrelide's highly potent PDEIII inhibitory cardioactive metabolite. Such preparations have the potential to inhibit platelet-mediated cancer cell proliferation, tumour development and formation of cancer metastases without the unwanted cardiotoxicity usually associated with anagrelide.
