Doses will be increased in a stepwise fashion and the decision to do so will be made by the participating Investigators on the basis of DLT, PK and PD. The starting dose will be 360mg od. Should this dose not be safe the dose level may be reduced to 240mg od. Dosing will initially take place once a day, for 28 days, while later cohorts will investigate twice daily dosing. More than one DLT in a once daily dose cohort will not preclude investigation of twice daily dosing at a lower dose.