Yanhong Gu¹, Jiahua Miao¹, Weicheng Wang², Hua Jiang³,Junxing Huang⁴, Shibing Liao⁵, Xiaoqin Li⁶, Peifen Cai², Qian Li²

¹Department of Oncology, Wuxi No.2 People Hospital, ²Department of Oncology, The First Affiliated Hospital with Nanjing Medical University,³Department of Oncology, the Second People Hospital of Lianyungang, ⁴Department of Oncology, the Jiangsu Taizhou People Hospital, ⁵Jiangsu Hospital of Integrated Traditional Chinese and Western Medicine, ⁶the Affiliated Hospital with Jiangsu University

Objective:The prognosis for unresectable metastatic colorectal cancers is poor, and improved therapies are needed. Recent studies have shown the activated NLRP3 inflammasome was one of the machanism that responsible for the resistance to 5-FU. Andrographolide (Andro), a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata, has been shown to suppress the activation of NLRP3 inflammasome. This clinical trial is to explore the efficacy of capecitabine combined with andrographolide in unresectable metastatic colorectal cancers patients. Method:This is a multicenter, randomized, controlled clinical trial. 308 patients more than 65 years old with unresectable metastatic colorectal cancer will be enrolled. They will be randomly assigned to receive either capecitabine (control group) or capecitabine plus andrographolide (experimental group). Patients in the control group will receive up to 6 cycles of capecitabine (1250mg/m², p.o. bid, days 1 to 14 of each 21-day cycle). Patients in the experimental group will receive up to 6 cycles of capecitabine plus andrographolide (capecitabine: 1250mg/ m², p.o. bid,days 1 to 14 of each 21-day cycle; andrographolide :500mg,ivd qd,days 1 to 14 of each 21-day cycle).The primary end point was progression-free survival (PFS). While secondary endpoints include overall survival (OS), overall response rate (ORR), health-related quality of life (HRQoL). Result: Up to now, 15 patients have been accrued: capecitabine plus andrographolide (n=7) and capecitabine (n=8). In the capecitabine plus andrographolide cohort, 2 patients were evaluated as PR, 3 patients were evaluated as SD and 2 patients were evaluated as PD. In the capecitabine cohort, 3 patients were evaluated as SD, 5 patients were evaluated as PD. Conclusion: Andrographolide, in combination with capecitabine, is likely to represent a potential therapeuticstrategy for unresectable metastatic colorectal cancers.

Key Words: colorectal cancer  Fluorouracil  andrographolide