Individualized Dose Escalation of 5-FU for Gastrointestinal Cancer

Inclusion Criteria: * Age ≥ 18 years * Diagnosis of metastatic or locally advanced/inoperable colorectal cancer or non-colorectal gastrointestinal cancer (including cancers of the stomach, esophagus, appendix, small bowel, and ampulla) * Clinically appropriate staging imaging of the chest, abdomen, and pelvis performed within 30 days prior to registration * ECOG Performance Status: 0-1 Exclusion Criteria: * Any prior receipt of oxaliplatin or fluoropyrimidine chemotherapy (other than radiation-sensitizing fluoropyrimidine chemotherapy) * Prior receipt of systemic chemotherapy in the 6 months prior to Day 1 of Cycle 1 of FOX (other than radiation-sensitizing chemotherapy) * Known mismatch repair deficiency or microsatellite instability-high disease * Known dihydropyrimidine dehydrogenase (DPD) deficiency, as identified by clinically indicated screening * Any confirmed second malignancy that is likely to require systemic therapy during the course of the six-month study period, in the opinion of the enrolling investigator * Any of the following baseline laboratory abnormalities: * Absolute neutrophil count (ANC) \< 2,500/mm3 * Platelet count \< 100,000/mm3 * Hemoglobin \< 9 g/dL * Creatinine \> 1.5 x ULN * Total bilirubin \> 1.5 x ULN * AST/ALT \> 5 x ULN * Patients who are unable to provide informed consent * Patients who are pregnant or breastfeeding * Patients who are incarcerated, homeless, or have active substance use disorders