Safety of Trifluridine/Tipiracil in Patients With Dihydropyrimidine Dehydrogenase Deficiency Diagnosed With Metastatic Colorectal or Gastroesophageal Cancer

Inclusion Criteria22

• Patient must have signed and dated a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.
• Histological or cytological documentation of adenocarcinoma of the colon or rectum or gastroesophageal cancer (lower oesophagus, gastroesophageal junction and gastric)
• Synchronous or metachronous metastatic colorectal or gastroesophageal cancer
• Presence of at least one measurable lesion according to RECIST v1.1
• No prior therapy for metastatic disease
• known DPD deficiency defined as plasma uracil concentration≥16 ng/ml For plasma uracil concentration \[16-20\[ ng/ml, plasma uracil dosage must be repeated in the 7 days to confirm that plasma uracil concentration ≥16 ng/ml. If the second result is different (i.e; uracil concentration \<16 ng/ml), keep the favourable result, and do not include the patient if only the first plasma uracil concentration≥16 ng/ml.
• Age ≥18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Adequate bone marrow, renal and liver functions as evidenced by the following laboratory requirements within 7 days prior to study treatment initiation:
• Absolute neutrophil count (ANC) ≥ 1,500/ mm³ without biologic response modifiers such as granulocyte colony-stimulating factor (G-CSF), within 21 days before the start of study treatment
• Platelet count ≥100,000/mm³, without platelet transfusion within 21 days before the start of study treatment
• Hemoglobin (Hb) ≥9 g/dL, without blood transfusion or erythropoietin within 21 days before the start of study treatment
• Serum creatinine ≤1.5 x upper limit of normal (ULN)
• Glomerular filtration rate as assessed by the estimated glomerular filtration rate (eGFR) ≥50 mL/min per 1.73 m² calculated by the Modification of Diet in Renal Disease (MDRD) abbreviated formula
• Total bilirubin ≤ 1.5 x ULN
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement of their cancer)
• Alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5.0 x ULN for patients with liver involvement for their cancer and/or bone metastases)
• International normalized ratio (INR) ≤1.5 or prothrombin time (PT) ≤1.5 x ULN Note: Patients on stable dose (dose has not been changed in at least 28 days) of anticoagulation therapy will be allowed to participate if they have no sign of bleeding or clotting and INR / PT and PTT / aPTT test results are compatible with the acceptable benefit-risk ratio at the investigator's discretion. In such case, limits as noted would not apply
• For women of reproductive potential, negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test obtained within 7 days before the start of study treatment. Women not of reproductive potential are female patients who are postmenopausal or permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy)
• For women of childbearing potential and men, agreement to use an adequate contraception for the duration of study participation and up to 7 months following completion of therapy.
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
• Affiliation to the Social Security System (or equivalent).