Abstract 4675: Effect and safety of FOLFOXIRI+B-mab as preoperative chemotherapy for multiple liver metastases of colorectal cancer.
Authors: Ichikawa Yasushi , Goto Ayumu , Kobayashi Noriotoshi , Tokuhisa Motohiko , Ishikawa Takashi , Kondo Kenichi , Ishibe Atsushi , Watanabe Kazuteru , Ota Mitsuyoshi , Fujii Shoichi , Akiyama Hirotoshi , Tanaka Kuniya , Endo Itaru 
Published: August 2014

Abstract
Background; R0 resection for liver metastases of colorectal cancer is one of the promising treatment to improve prognosis of advanced colorectal cancer. Powerful regimen FOLFOXIRI including 3 cytotoxic drugs; 5FU, irinotecan and oxaliplatin was reported as promising treatment for advanced colorectal cancer (J Clin Oncol 2007; 25: 1670-76). 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 chemotherapy has been conducted now, and Phase I was concluded. In this study, we report effect and safety of FOLFOXIRI+B-mab in Phase I study. 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. Results: Currently, 9 patients were enrolled. In level 1, 1 patient showed Grade 3 diarrhea as dose-limiting toxicity and for the other 5 patients 150 mg/m2 of irinotecan was tolerable. In level 2, 2 patients showed DLT; one was Grade 3 diarrhea in the 1st cycle and the other one was febrile neutropenia in the 2nd cycle. Then 180 mg/m2 of irinotecan was over the MTD. Then Phase I study was concluded and recommend dose of irinotecan was decided as 150 mg/m2. In all adverse event, Grade 3/4 neutropenia was detected in 66%. Excluding hematological toxicity, Grade 3 or worse adverse event was 2 cases of Grade 3 diarrhea. In the 6 patients, one patient have dropped out, 4 patients were performed R0 resection and one patient could not be performed R0 resection after 6 cycles of regimen. All 5 patients showed PR and average of reduction rate was 62.7%. There was no pathological CR in the 4 patients who was performed R0 resection. There was no severe postoperative complication in them. Conclusion: This regimen is safe and shows high PR rate. So, the regimen is effective and improve R0 resection rate for multiple liver metastases of colorectal cancer. Further investigation of this study is still ongoing now.
Citation Format: Yasushi Ichikawa, Ayumu Goto, Noriotoshi Kobayashi, Motohiko Tokuhisa, Takashi Ishikawa, Kenichi Kondo, Atsushi Ishibe, Kazuteru Watanabe, Mitsuyoshi Ota, Shoichi Fujii, Hirotoshi Akiyama, Kuniya Tanaka, Itaru Endo. Effect and safety of FOLFOXIRI+B-mab as preoperative chemotherapy for multiple liver metastases of colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4675. doi:10.1158/1538-7445.AM2013-4675