Pharmacogenomics (PGx) is the study of how genes affect a person's response to drugs. PGx testing for certain genes can help predict the risk of side effects from chemotherapy agents. Testing is not regularly performed in clinical practice due to long wait times for results and challenges with integrating test results in the electronic health record. Investigators leading this study hope to find out if providing cancer care providers with the ability to order a PGx test and electronically receive results with dosing recommendations will increase the use of these tests to guide treatment decisions and improve patient outcomes.

This is a non-randomized implementation study, which means that all participants in this study will undergo genotyping for a pharmacogenetic test. The investigators will primarily measure the feasibility of using this test to guide cancer care.

Inclusion Criteria:

1. Able and willing to provide informed consent
2. Male or female, aged 18 years or older at the time of study initiation
3. Pathologically confirmed gastrointestinal malignancy for which treatment with a fluoropyrimidine and/or irinotecan is indicated
4. Willing to undergo blood or saliva sampling for PGx testing and comply with all study-related procedures
5. Life expectancy of at least 6 months

Exclusion Criteria:

1. Prior treatment with irinotecan

2. DPYD or UGT1A1 genotype already known

3. Severe renal or hepatic impairment (or unacceptable laboratory values), including:

   • Neutrophil count of <1.5 x 109/L, platelet count of <100 x 109/L
   • Hepatic function as defined by serum bilirubin >1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) >2.5 x ULN, or in case of liver metastases ALT and AST>5 x ULN
   • Renal function as defined by serum creatinine >1.5 x ULN, or creatinine clearance <60 ml/min (by Cockcroft-Gault Equation)

4. Women who are pregnant or breast feeding, or subjects who refuse to use reliable contraceptive methods throughout the study

5. Treating physician does not want subject to participate

Data will be made available upon reasonable request.

Study protocol, SAP, ICF will be made available 1 year following enrollment of the last participant. IPD will be made available 6 months after publication of study results.

Contact PI, Sony Tuteja, PharmD, sonyt@pennmedicine.upenn.edu with individual requests.

Adverse event data was collected during the first six cycles of chemotherapy, <6 months.

Severe adverse events were defined as any related event requiring hospitalization, emergency room visits, oncology evaluation center care, or death. Other adverse events are all other adverse events that were collected that did not meet the serious criteria. Events were primarily assessed through medical records review.