Abstract 3693: Power of FOLFOXIRI+B-mab as preoperative chemotherapy for multiple liver metastases of colorectal cancer -Relationship between clinical response and pathological response-

Abstract

Abstract Background; R0 resection for liver metastases of colorectal cancer is one of the promising treatment to improve prognosis of advanced colorectal cancer. Recently, effective anti-cancer drugs and various regimens using them were created and some advanced inoperable liver metastases were converted to operable by those chemotherapy (CT). Therefore, development of powerful regimens to shrink liver metastases strongly is an important issue. In our department Phase I/II study of FOLFOXIRI+B-mab including fluoroiuracil/oxaliplatin/irinotecan/bevacizumab for advanced liver metastases of colorectal cancer as pre-operative CT has been conducted now. In this study, this regimen's effect on shrinkage of liver lesions from gross view of clinical response and micro view of pathological response are evaluated. Methods: The study was designed as a single-arm, open-label phase I/II trial. Phase I was conducted as sequential dose escalation to define the maximum-tolerated dose (MTD) of irinotecan. Patients who are colorectal cancer with 4 or more liver metastases and no other distant metastases are included. The regimen includes bevacizumab; 5 mg/kg, oxaliplatin; 85 mg/m2, l-LV; 200 mg/m2, 5FU; 400 mg/m2 administered on day 1, followed by 5FU; 2400 mg/m2 continuously administered for 46 hours. Dose escalation of Irinotecan was planned from level 1; 150 mg/m2, level 2; 180 mg/m2 and level 0; 125 mg/m2. In Phase II, R0 resection rate of liver metastases as primary endpoint will be evaluated using MTD of irinotecan estimated in Phase I. After 6 cycles of the CT, R0 operability was evaluated. Now 6 patients were studied in level 1 dose, in them, one patient dropped out because of DLT, 4 were converted to R0 resection and another is waiting for resection. To evaluate power of this regimen, macroscopic and microscopic response of resected hepatic lesions of these 4 patients were investigated. Results: Median number of metastases of each patient was 9 (4-21). Total number of metastases of the 4 patients was 43. Median long span of the all tumors was 12 mm (5-76 mm). All 4 patients showed PR in CT and median of reduction rate was 38% (34-67%). Four tumors (9.3%) showed clinical CR. Twelve tumor (27.9%) showed pathological CR, 26 (60.5%) were moderate response (2/3 or more of tumor showed necrosis or disappear), and only one (2.3%) was mild response. Conclusion; FOLFOXIRI+B-mab showed powerful effect to shrink liver metastases of colorectal cancer. It is a good regimen for pre-operative CT for liver metastases. Further investigation of this study is still ongoing now. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3693. doi:1538-7445.AM2012-3693