Clinical Trail Of "Aifuling" In Patients With Advanced Hepatocellular Carcinoma

PurposeThis clinical trial of "Aifuling", a new anti-tumor agent in Macau, assessed efficacy and toxicity of this drug in advanced hepatocellular carcinoma (HCC) patients.Principal constituent of Aifuling is Cucurbitacin,0.2g/cap (Each capsule contains180μg cucurbitacin B). The content is a transparent oily liquid of colorless to light yellow, which is bitter. It is indicated for the treatment of cancer patients, including primary liver cancer, lung cancer, breast cancer, pancreas cancer, etc. This nagent should be taken orally,1capsule every8hours or as instructed by physician. A course of treatment should extend over3months. It is forbidden in cases of serious digestive tract ulcer and pregnancy.The mechanism of AiFuLing on primary liver cancer is by down-regulating p-STAT3of liver cancer cells, thus inducing their apoptosis. Current studies suggested that cucurbitacin can improve liver function, such as correcting inverse proportion of albumin/globulin, reducing pleural effusion and pyoperitoneum, promoting regrowth of liver cells, reducing liver fibrosis, and eliminating jaundice. Therefore achieving the effect of improving quality of life and extending survival time.MethodsPatients with HCC, with or without prior systemic treatment, and Child-Pugh (CP) A or B, stage ⅢB/Ⅳ, were given continuous, sublingual "Aifuling"0.2g every8hours in4-weeks cycle, for3cycles. Tumor response was assessed every6weeks by Response Evaluation Criteria in Solid Tumour. Toxicity was assessed by The National Cancer Institute general toxic standards (NCI-CTC3.0). Primary endpoints were DCR (Disease control Rate) and PFS (Progression-free Survival), secondary endpoint was OS (Overall Survival).ResultFrom July2010to March2012, there were29patients enrolled,4of which quited, and4dropped-out. Of21patients treated,95%were male, aged from38to73years, median aged was57. There were8patients with ECOG PS1,12patients with ECOG PS2, while1patient got3. And there were14patients infected by HBV while no patient infected by HCV. Most of these patients had Child-Pugh (CP) A (n=14,66%),7patients had CP B. All these patients were at advanced stage.By1st March2012, the median time of treatment for these21patients was3.3months. No patient reduced dose due to drug-related toxicity. Of21patients treated,2(10%) patients achieved partial response, nine (43%) patients had stable disease, three (14%) patients had progressive disease, and disease control rate was52.4%. Investigator-assessed median progression-free survival was3.7months, and the overall survival was5.3months. There were no significant grade3/5drug-related toxicities. Grade1/2drug-related toxicities was diarrhea (5%and10%).ConclusionSingle-agent "Aifuling" has modest efficacy in patients with HCC, those with or without prior systemic treatment, and Child-Pugh (CP) A or B, stage ⅢB/Ⅳ. Aifuling has low toxicity and was well tolerated, it is worth to study "Aifuling" deeper.