Comparison of the Pathological Effect Between 2 and 4 Cycles Neoadjuvant CAPOX for Low/Intermediate Risk II/III Rectal Cancer

Neoadjuvant Chemotherapy alone has showed much benefit for low/ intermediate risk stage II/III rectal cancer which would be verified by the PROSPECT trial. However, the effect of the Neoadjuvant chemotherapy was heterogeneous in different patients. It's important to verify those chemo-resistant cases as early as possible. So that, this trial will compare the pathological effect between 2 cycles and 4 cycles of Capox regimen as neoadjuvant chemotherapy for low/ intermediate risk stage II/III rectal cancer to explore whether those chemotherapeutic non-responders after 2 cycles Capox was non-inferior to those after 4 cycles chemotherapy.

Inclusion criteria

• Age: 18-75 years old; No gender limitation;
• Patients diagnosed with low/intermediate risk stage II/III rectal cancer under MRI and transanal ultrasound,defined as: low:T3a-bN0-1M0, EMVI (±), MRF (-) (≥2mm); Middle-high rectal cancer: T3a-cN0-1M0, EMVI (±), MRF (-) (≥2mm); No more than 3 lymph nodes with short diameter over 8mm or highly suspected metastases; Patients with very low rectal cancer who met the above criteria and could achieve negative circumferential resection margin under ELAPE surgery could be included in the group
• tumor located <=12cm from anal verge by colonoscopy or anal examination
• no distant metastasis confirmed by CT examination;
• rectal adenocarcinoma confirmed by pathology,
• ECOG score: 0-1;
• Patients with primary rectal cancer who did not receive surgery (except palliative stomy), radiotherapy, systemic chemotherapy or other anti-tumor therapy before enrollment;
• Main organs function normally, that is, meet the following characteristics: ① Blood routine examination criteria should meet: Hb ≥9g/dL, WBC ≥ 3.5/4.0×109/L, neutrophils ≥ 1.5×109/L, PLT≥ 100×109/L. ② Biochemical tests should meet the following criteria: CREA and BIL ≤ 1.0 times upper limit of normal (ULN), ALT and AST≤ 2.5 times upper limit of normal (ULN), alkaline phosphatase (ALP) ≤2.5×UNL, total bilirubin (TBIL) ≤1.5×UNL.
• No history of allergy to platinum drugs when no 5-FU drugs are allergic;
• Women of childbearing age must have had a pregnancy test (serum or urine) 7 days prior to enrolment, be negative, and be willing to use an appropriate method of contraception during the trial and 8 weeks after the last dosing. For men, surgical sterilization or consent to use an appropriate method of contraception during the trial or for 8 weeks after the last dosing;
• Subjects volunteered to participate in this study, signed the informed consent, and showed good compliance and followed up.

Exclusion criteria

• patients suspect to Lynch syndrome;
• Patients showed distant metastasis during treatment;
• Previously or coexisting malignancies (including concurrent colon cancer), except for cured basal cell carcinoma of the skin and carcinoma in situ of the cervix;
• pregnant or breastfeeding women;
• Patients with severe cardiovascular diseases and diabetes that is not easily controlled;
• People with mental disorders;
• Severe infection;
• sever renal disfunction;
• History of gastrointestinal fistula, perforation, bleeding, or severe ulcer;
• Allergic to 5-FU or platinum;
• The presence of serious gastrointestinal diseases that affect the absorption of oral chemotherapeutic drugs; (12) Participants in additional clinical trials within 4 weeks prior to the start of treatment.