maintenance chemotherapy with s-1 vs. observation after adjuvant therapy for resected pancreatic cancer with high risk of recurrence/metastasis

Conditions: Pancreatic Cancer; Postoperative Adjuvant Therapy; Maintenance Therapy

Summary: the goal of this real-world study is to learn if maintenance chemotherapy with tegafur, gimeracil, and oteracil potassium (s-1) can improve disease-free survival (dfs) compared to follow-up observation in patients with resected pancreatic cancer at high risk of recurrence or metastasis after adjuvant therapy. the main questions it aims to answer are: * does maintenance therapy with s-1 improve disease-free survival (dfs) compared to follow-up observation after standard treatment for resected high-risk pancreatic cancer? * does s-1 maintenance therapy improve overall survival (os), distant disease-free survival (ddfs), and local recurrence-free survival (lrfs) compared to observation? * what are the safety and tolerability profiles of s-1 maintenance therapy compared to observation? researchers will compare two groups: the s-1 maintenance therapy group and the observation-only group, to see if s-1 improves survival outcomes and safety. participants will: * receive maintenance chemotherapy with s-1 based on body surface area dosing or be assigned to the observation group without drug intervention. * undergo imaging evaluations every 12 weeks to monitor for disease recurrence or metastasis. * report side effects and any adverse events during the study.


Eligibility criteria:
inclusion criteria: 1. histologically confirmed pancreatic cancer (originating from the pancreatic ductal epithelium); 2. meets one of the following conditions: pathologically confirmed as moderately differentiated, moderately to poorly differentiated, or poorly differentiated; or pathologic staging as: t3n0m0, t1-3n1-2m0, t4n0-2m0; or one or more surgical margins are r1 resected (r0 resection if no tumor cells are found more than 1mm from the margin, otherwise r1 resection); or involvement of the portal vein and/or superior mesenteric vein resection; or pre-adjuvant chemotherapy ca19-9 \> 90 u/ml; or pre-adjuvant chemotherapy ctdna testing positive; 3. completed standard treatment: received radical resection, postoperative adjuvant therapy (including adjuvant chemotherapy based on gemcitabine or fluorouracil), and radiotherapy (if applicable); 4. eligible for oral medication; 5. age ≥18 and ≤75, male or female; 6. ecog performance status: 0 to 2; 7. normal function of major organs as per the following criteria within 14 days prior to starting treatment:① neutrophil count ≥ 1.5×10\^9/l;② platelet count ≥ 75×10\^9/l;③ hemoglobin ≥ 9.0 g/dl;④ ast ≤ 2.5×unl (upper normal limit) (if liver metastasis present, ast ≤ 5×unl);⑤ alt ≤ 2.5×unl (if liver metastasis present, alt ≤ 5×unl);⑥ total bilirubin ≤ 1.5×unl;⑦ creatinine clearance (calculated using the cockcroft-gault formula) \> 60 ml/min or serum creatinine ≤ 1.5×unl; 8. women of childbearing potential must have used reliable contraception within 7 days prior to enrollment and have a negative pregnancy test, and must be willing to use appropriate contraception during the study and for 6 months after the last dose of the investigational drug. for men, they must be surgically sterile or agree to use appropriate contraception during the study and for 3 months after treatment; 9. expected survival time ≥6 months; 10. voluntary participation in the study, signed informed consent, and demonstrated good compliance and cooperation during follow-up. exclusion criteria: 1. pancreatic cancer originating from non-pancreatic ductal epithelium, including pancreatic neuroendocrine tumors, pancreatic acinar cell carcinoma, pancreatoblastoma, and solid-pseudopapillary tumor; 2. incomplete macroscopic resection (r2 resection); 3. presence of distant metastasis (including malignant ascites and pleural effusion, peritoneal metastasis) or locally recurrent pancreatic cancer; 4. ca19-9 \> 180 u/ml within 21 days before enrollment; 5. severe liver dysfunction (ast/alt \> 3.5 times the upper limit of normal, alkaline phosphatase \> 6 times the upper limit of normal), with liver drainage; 6. known peripheral neuropathy (ctcae ≥ grade 2); 7. participation in another clinical trial of cytotoxic drugs, targeted therapies, immunotherapies, etc., within the past 4 weeks, or received systemic chemotherapy, radiotherapy, or biological therapy within the past 4 weeks; 8. concurrent or metachronous cancers with disease-free survival ≥ 5 years (excluding pancreatic cancer), except for cancers that have been cured or can be potentially cured with local excision (e.g., esophageal cancer, gastric cancer, colorectal cancer, cervical cancer, non-melanoma skin cancer, bladder cancer); 9. factors that significantly affect oral drug absorption, such as difficulty swallowing, chronic diarrhea, or gastrointestinal obstruction; uncontrolled crohn's disease or ulcerative colitis; 10. clinically symptomatic serous effusions (including pleural effusion, ascites, pericardial effusion) requiring symptomatic treatment; 11. pregnant or breastfeeding women; patients of childbearing potential unwilling or unable to take effective contraceptive measures; 12. known allergy to the investigational drug, the class of the investigational drug, or its components; 13. need for systemic corticosteroid treatment (except for local steroid pre-treatment); 14. history of interstitial lung disease (including interstitial pneumonia, pulmonary fibrosis, etc.) or ct findings of interstitial lung disease; 15. active local or systemic infection requiring treatment; 16. heart failure nyha classification ≥ ii or severe heart disease; 17. known hiv infection or history of acquired immunodeficiency syndrome (aids) or active hepatitis b or c; 18. toxicity not recovered (ctcae \> grade 1) or previous anticancer surgery not fully recovered; 19. patients deemed unsuitable for this study by the investigator.

Keywords: maintenance therapy s-1