mFOLFOXIRI Versus mFOLFOX6 as Adjuvant Chemotherapy for Locally Advanced Colorectal Cancer
Status:
Recruiting
Trial end date:
2025-02-01
Target enrollment:
Participant gender:
Summary
The current standard treatment for locally advanced rectal cancer is still fluorouracil-based
neoadjuvant radiotherapy and chemotherapy followed by TME surgery, followed by adjuvant
chemotherapy. Fluorouracil single-agent simultaneous sensitization of radiotherapy and
chemotherapy has a pCR of about 15-20% and a tumor downgrade (ypStage 0-I) rate of about 35%.
However, about 30% of patients still have distant metastasis, which is the main obstacle
affecting the survival prognosis of patients with locally advanced rectal cancer.
About 50% -65% of patients was still stage II-III after neoadjuvant therapy. The long-term
follow-up shows that for patients with ypT4 after surgery, the 3-year DFS is about 50%. For
patients with ypN2, the 3-year DFS is less than 40%. Therefore, it is necessary to strengthen
postoperative adjuvant chemotherapy to improve the survival prognosis for these patients.
Although FOLFOX adjuvant chemotherapy improved survival benefit than 5FU as adjuvant
treatment in ypStage II-III patients after neoadjuvant treatment in ADORE trial. However,
with the progress of neoadjuvant therapy research, more and more studies have proposed to
move part or all of postoperative adjuvant chemotherapy to preoperative neoadjuvant therapy
due to low compliance of adjuvant chemotherapy.
During neoadjuvant treatment, induction chemotherapy with FOLFOX / CAPEOX or consolidation
therapy after CRT with FOLFOX / CAPEOX had been investigated a lot. The pCR rate was 19%
-38%, and the tumor downstaging rate was about 50%. Another 50% of patients still had ypstage
II-III postoperatively. The 3-year DFS for ypStage III was only 55% even with FOLFOX as
adjuvant chemotherapy. And for ypT4N0 patients with ypstage IIB-IIC, there is also a higher
risk of recurrence and metastasis. And it is urgent to explore new treatment strategies to
improve this part of patients Survival prognosis.
For locally advanced colon cancer, surgery combined with postoperative adjuvant chemotherapy
is currently the standard treatment mode for stage II-III colon cancer. About 30% of patients
with locally advanced disease will relapse within 3 years, of which distant metastases are
more common and eventually become the main cause of death of patients. For locally advanced
colon cancer with a preoperative staging of T4b, the NCCN guidelines recommend surgery after
neoadjuvant chemotherapy with FOLFOX or CAPOX regimens. In the FOxTROT study of neoadjuvant
treatment of locally advanced colon cancer, for patients with T3> 5mm or T4, after 4 courses
of neoadjuvant chemotherapy with FOLFOX regimen, 20.5% of patients still have T4 after
surgery, and 15.2% of patients had N2 disease. For this part of patients, new postoperative
treatment options should also be explored to improve patient survival and prognosis.
In view of the high efficiency of the three-agent FOLFOXIRI regimen in advanced colorectal
cancer and the success in adjuvant chemotherapy after pancreatic cancer surgery, 5FU,
oxaliplatin combined with irinotecan may have a synergistic effect. At present, a phase III
randomized controlled study (IROCAS study) in Europe is underway. For high-risk phase III
patients, the mFOLFOXIRI regimen is compared with mFOLFOX6 regimen adjuvant chemotherapy.
Based on the above reasons, our center plans to further carry out "multi-center, randomized,
controlled phase III clinical study of mFOLFOXIRI versus mFOLFOX6 adjuvant chemotherapy after
neoadjuvant oxaliplatin in locally advanced colorectal cancer." Improve the survival
prognosis of postoperative high-risk colorectal cancer patients after neoadjuvant therapy.