Prospectively Randomized Control Clinical Trial of FOLFOXIRI Preoperative Chemotherapy Alone on Rectal Cancer in Local Advance Comparing to Oral Capecitabine Combined With Long-term Radiation
Preoperative radiation and chemotherapy is the standard treatment for local advanced rectal cancer. The addition of oxaliplatin to capecitabine combined with radiotherapy does not improve local control and long-term survival. Most importantly,chemoradiotherapy significantly increased surgical complication and poor long-term quality of life .In the absence of effective measures of predicting chemo-sensitivity, there is considerable risk of using any two-drug regimen for neoadjuvant therapy. Simultaneous use of the three chemotherapeutic drugs may be able to reduce the likelihood of resistance to both dual drug regimen and single drug regimen. The purpose of this study is to compare the efficacy and safety of three chemotherapeutic regimen known as FOLFOXIRI (the drug 5-fluorouracil, oxaliplatin, Irinotecan) with standard radiotherapy combined with capecitabine in neoadjuvant therapy for local advanced rectal cancer. The drugs in the FOLFOXIRI regimen are all FDA(Food and Drug Administration) approved and have been used routinely to treat patients with advanced colorectal cancer.
• 1）Age: 18 to 75 years old;
• 2）Histological diagnosis of rectal adenocarcinoma;
• 3）Distance form anal margin ≤ 5cm: cT3-4aN + M0, there is no distant metastasis, lymph node positive, or the tumor breaking through the muscular layer, no invasion of the adjacent organs , positive MRF, it is estimated that R0 resection can be performed;
• 4）From the anal margin\>5cm: cT3c-4aN+M0, there is no distant metastasis, lymph node positive, or the tumor breaking through the muscular layer with invading the mesorectum more than 5mm, no invasion of the adjacent organs, positive MRF, it is estimated that R0 resection can be performed;
• 5）Preoperative staging method: All patients undergoing anal examination, high-resolution MRI and/or EUS for preoperative staging. The diameter of parenteral lymph node ≥10mm, lymph node shape or the MRI characteristics is consistent with typical lymph node metastasis. If combined with EUS, the material should be submitted to the central assessment team for judgment when there is a contradiction in the staging method. Preoperative chest and abdomen CT, pelvic MRI are used for excluding distant metastasis;
• 6）Confirmed as the lower edge of tumor is located within 12 cm from the anal margin by MRI examination
• 7）There is no signs of intestinal obstruction, or obstruction of intestinal after treating with proximal colostomy has been relieved;
• 8）Patients did not previously receive rectal surgery, chemotherapy or radiation therapy , biological treatment , except for endocrine therapy;
• 9）ECOG Performance Status :0-1
• 10）Life expectancy: more than 2 years;
• 11）Laboratory values：Hematology: white blood cell count\>4000/mm3; Platelet count\>100000/mm3; Hemoglobin \>10g/dL; Liver function: SGOT and SGPT \< 1.5 upper limit of normal(ULN); Bilirubin\< 1.5mg/dL; Renal function :Creatinine \<1.8mg/dL.