98 Background: Neoadjuvant chemoradiotherapy (CRT) is the standard of treatment for locally advanced rectal cancer, but it delays administration of systemic chemotherapy, leading to high incidence of distant metastases. To enhance systemic chemotherapy and avoid the damage of radiation, neoadjuvant chemotherapy with mFOLFOXIRI had been investigated. However, no randomized comparison assessing the efficacy of mFOLFOXIRI versus CRT in LARC. Methods: 145 LARC patients received CRT as neoadjuvant treatment in the phase III FOWARC study (NCT01211210) and 103 patients received mFOLFOXIRI alone preoperatively in a phase II study (NCT02217020). A propensity score-adjusted method was adopted to provide an estimation of the benefit from the enhancive chemotherapy regimen as neoadjuvant treatment in terms of survival and activity parameters. Results: In the original cohort, patients in the mFOLFOXIRI group were younger with the median age of 48 versus 56 years old in the CRT group. More patients with tumor length over 5 cm and cT3 or N2 disease in the mFOLFOXIRI group ( P< 0.05). After propensity score adjusted matching, 73 patients were comparable in each groups. The pCR rate was 23.3% in thd mFOLFOXIRI group versus 13.7% in the CRT group, respectively (P = 0.14). The proportion of ypStage 0-I was 45.2% versus 39.7%, respectively (P = 0.5). The local recurrence rate was comparable between the two groups (5.5% vs. 4.1%, P= 0.70). But mFOLFOXIRI decrease the incidence of distant metastasis (8.2% vs. 27.4%, P= 0.002). And the 3 year disease free survival was 86.8% in the mFOLFOXIRI group versus 75.8% in the CRT group, respectively ( P= 0.049). Lower incidence of anastomotic fistula was shown in mFOLFOXIRI alone group than that of CRT group (5.5% vs. 17.8%, P = 0.02). Grade 3/4 neutropenia was more commen in mFOLFOXIRI group (39.7% vs. 8.2%, P < 0.001). Conclusions: Comparing with CRT, preoperative mFOLFOXIRI decreased the incidence of distant metastasis and improved 3 year DFS, and led to less toxicity and fewer postoperative complications. The phase III randomized study comparing FOLFOXIRI with CRT is still ongoing. Clinical trial information: NCT01211210 and NCT02217020.
Neoadjuvant treatment with mFOLFOXIRI alone versus chemoradiotherapy in locally advanced rectal cancer: A propensity score analysis from two prospective trials
