Use of Trifluridine/Tipiracil and Oxaliplatin as Induction Chemotherapy for the Treatment of Resectable Esophageal or Gastroesophageal Junction (GEJ) Adenocarcinoma

Prior treatment

• Prior chemotherapy, thoracic radiotherapy or prior surgical resection for an esophageal tumor
• Any concurrent active malignancy that requires active systemic intervention
• Participants who have had major surgery or field radiation within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Received an investigational agent within 4 weeks prior to enrollment
• Patient previously treated by TAS 102 or history of allergic reactions attributed to compounds of similar composition to TAS 102 or any of its excipients

Other illness

• Participants with known metastatic disease
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Grade 3 or higher hypersensitivity reaction to oxaliplatin or grade 1-2 hypersensitivity reaction to oxaliplatin not controlled with premedication
• Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug

Lab values

• Hereditary problems of galactose intolerance; e.g., Lapp lactase deficiency or glucose galactose malabsorption

Other

• Grade 2 or higher peripheral neuropathy
• Pregnant or nursing female participants
• Unwilling or unable to follow protocol requirements

• Must have histologically proven loco-regional esophageal or gastroesophageal junction adenocarcinoma
• Endoscopic ultrasound (EUS), or clinically determined node-positive disease with any T-stage or T3-T4a with any N stage: Patients with EUS T4b and any M1 cancer will not be included
• Must have potentially resectable disease
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Hemoglobin \>= 9 g/dL
• Absolute neutrophil count \>= 1500/mm\^3
• Platelet count \>= 100,000/mm\^3
• Creatinine \< 1.5 upper limit of normal (ULN)
• Bilirubin \< 1.5 x ULN
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3 x ULN
• Capacity to take oral tablet(s) without difficulty
• Participants of child-bearing potential must agree to use highly effective contraceptive methods (e.g., hormonal plus barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure