Irinotecan Liposomes in Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer

Inclusion criteria

• Age ≥ 18 years and ≤ 75 years, both male and female are eligible;
• Histologically confirmed rectal adenocarcinoma;
• Clinical stage assessed by MRI as T3-4 or N+ (according to the 8th edition of the AJCC);
• Distance from the lower edge of the tumor to the anal verge ≤ 10 cm;
• ECOG (Eastern Cooperative Oncology Group) performance status of 0-1;
• UGT1A1*6 and UGT1A1*28 gene phenotypes are either wild-type (GG+6/6) or single-site mutant (GG+6/7 or GA+6/6);
• No prior anti-tumor treatment for rectal cancer, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.;
• Normal function of major organs.

Exclusion criteria

• Previous or ongoing treatment for rectal cancer, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.
• Known MSI-H (high microsatellite instability) by genetic testing or dMMR (deficient mismatch repair) by immunohistochemistry.
• Known hypersensitivity, allergic reaction, or contraindication to irinotecan liposomes/vehicle, irinotecan, other liposomal products, 5-FU, leucovorin, oxaliplatin, or any of these agents.
• Uncontrolled cardiac symptoms or disease.
• Severe infection (CTCAE > Grade 2) within 4 weeks prior to the first use of the study drug, such as severe pneumonia requiring hospitalization, bacteremia, or infectious complications; baseline chest imaging showing active pulmonary inflammation; signs and symptoms of infection within 14 days prior to the first use of the study drug or requiring oral or intravenous antibiotic therapy, excluding prophylactic use of antibiotics.
• Severe gastrointestinal dysfunction (inflammation or diarrhea greater than Grade 1).