Individualized Dose Escalation of 5-FU for Gastrointestinal Cancer

Inclusion Criteria:

• Age ≥ 18 years

• Diagnosis of metastatic or locally advanced/inoperable colorectal cancer ornon-colorectal gastrointestinal cancer (including cancers of the stomach, esophagus,appendix, small bowel, and ampulla)

• Clinically appropriate staging imaging of the chest, abdomen, and pelvis performedwithin 30 days prior to registration

• ECOG Performance Status: 0-1

Exclusion Criteria:

• Any prior receipt of oxaliplatin or fluoropyrimidine chemotherapy (other thanradiation-sensitizing fluoropyrimidine chemotherapy)

• Prior receipt of systemic chemotherapy in the 6 months prior to Day 1 of Cycle 1 ofFOX (other than radiation-sensitizing chemotherapy)

• Known mismatch repair deficiency or microsatellite instability-high disease

• Known dihydropyrimidine dehydrogenase (DPD) deficiency, as identified by clinicallyindicated screening

• Any confirmed second malignancy that is likely to require systemic therapy duringthe course of the six-month study period, in the opinion of the enrollinginvestigator

• 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