 - Patients with significant visceral fluid collections including ascites, pericardial effusions, pleural effusions or others may experience delayed clearance of methotrexate because of third space accumulation which could result in methotrexate toxicity and inability tolerate the proposed study treatment. While these are not absolute exclusions the Study Chair or co-Chairs should be contacted to discuss possible enrollment. Patients with significant ascites defined as European Association for the Study of the Liver grade 2, or with asymptomatic pleural effusions with an estimated size 200 mL, or with symptomatic pleural effusion of any size will be excluded. 