Any of the following underlying diseases including:1. History or evidence of severe cardiac disease(e.g. NYHA Functional Class III or IV - see Appendix 2), clinical or medical history of unstable angina, acute coronary syndrome, myocardial infarction or revascularization within 6 months, ventricular tachyarrhythmias requiring ongoing treatment 7. History or evidence of clinically significant peripheral vascular disease, such as intermittent claudication or prior amputation 8. History or evidence of clinically significant impaired renal or hepatic function 8. Stroke (within 12 months of study entry) 9. Any major surgical procedure within one month of study entry 10. Significant media opacities, including cataract, which might interfere with visual acuity, assessment of toxicity. Subjects should not be entered if there is likelihood that they will require cataract or glaucoma surgery in either eye during the study treatment and follow-up period.