天津第一中心医院发表在Hepatology上面一篇肝癌肝移植术后使用利卡汀的文章。仅把讨论部分发上来。
题目：A randomized controlled trial of licartin for preventing hepatoma recurrence after liver transplantation
Discussion
Our preclinical work and phase 1/2 trials have demonstrated that Licartin can accumulate in HCC lesions and is safe and effective in the treatment of HCC.[17-20][32][33] In the present study, Licartin was well tolerated and effective in decreasing the recurrence of HCC and prolonging the survival of patients with advanced HCC after OLT. Compared with that of the control group, 1 course treatment of Licartin significantly reduced the 1-year recurrence rate by 30.4%, and significantly increased the 1-year survival rate by 20.6%. The pretransplantation AFP level was found to be associated with both recurrence and survival. The patients in the treatment group obtained an earlier decrease of the basal abnormal AFP level and a longer period of normal AFP level than the patients in the control group, suggesting a better prognosis.
OLT is believed to be the only possible curative therapeutic option for unresectable HCC with underlying cirrhosis. But some discouraging experiences and the lack of donor liver grafts require the medical community to accurately define the patient population or to develop some multimodality therapy, such as pretransplant loco-regional treatment, pretransplant, intratransplant, and posttransplant systemic chemotherapy, and immunosuppressive protocol.[34] Pretransplant loco-regional treatment has to some extent prevented tumor progression in patients on the waiting list for transplantation, other multimodality protocols have either fallen out of favor or need further randomized controlled trials to confirm their effects, with the emphasis on preventing recurrence by imposing strict selection criteria.[7][35-38] Milan criteria were widely used and warranted good outcome in a strictly selected but small group of patients with HCC. At present, about 10% recurrence was seen in those patients meeting the Milan criteria, while rates as high as 50% were reported in those patients with tumors more than 5 cm in size and with portal vein invasion.[10][39] In the present study, the 1-year recurrence rate in control-group was 57.1%, which was similar to that reported previously (50%), while that in the treatment group was 26.7%, which was significantly decreased compared with that in the control group.
For a patient with HCC treated by transplantation, 1-year survival rates of 77%-80% could be expected when the Milan criteria is met.[40] Recently, some researchers have questioned whether the criteria might be safely extended.[14][38] Using extended criteria (single tumor less than 6.5 cm in size, or more than 3 tumors, the largest less than 4.5 cm, and a total diameter for all tumors less than 8 cm), Yao et al. reached a 1-year survival of 90%. But in China, it was reported that all the patients with stage 3 or 4 HCC suffered recurrence in 3-6 months after OLT, and the average survival time was 4.5 months.[41][42] In this study, all the patients had stage 3 or 4 HCCs and large-size tumors or more lesions. Posttransplant Licartin treatment achieved the 1-year survival rate of 82.5%, which was similar to the current expected 1-year survival rate for a patient with HCC who has been transplanted (77%-80%).[40]
To our knowledge, the present study is the first prospective randomized controlled trial to evaluate the clinical efficacy of antibody targeting radioimmunotherapy in preventing tumor recurrence and prolonging survival after OLT in patients with advanced HCC with larger tumor size and more tumor lesions than that in Milan criteria or in some reported expanded criteria. The clinical efficacy of Licartin may be attributed to 2 possible mechanisms. HAb18G/CD147, the target antigen, was recently found to be involved in HCC invasion and metastasis in vitro and in vivo. Licartin could specifically bind to HAb18G/CD147 and effectively inhibit HCC metastasis (Chen ZN, unpublished data). In the present work, Licartin may exert its effect by blocking the function of HAb18G/CD147. Furthermore, it may also function through its high affinity and specific binding to HAb18G/CD147 on HCC cells and the carried radionuclide 131I. It is generally believed that the high risk factor for HCC metastasis and recurrence is the escaped tumor cells in the circulation.[43] Licartin may efficiently target and bind to the escaped HCC cells in the circulation or homing cells to liver by the antigen-antibody specific recognition and thus allow the carried radionuclide to destroy the target site and to kill the cells.
In this study, the 1-year recurrence in the treatment group (26.7%) is still higher than that seen with Milan criteria (10%), but the 1-year survival in the treatment group (82.5%) is comparable with that seen with Milan criteria (77%-80%). Because most patients with HCC fail to meet Milan criteria, this study provides information about whether they can benefit from OLT when they have no other better therapeutic choices and have a suitable donor liver. The combination of Licartin with other treatments, such as chemotherapy, may also be a promising direction in antirecurrence therapy of advanced HCC after OLT. If this evidence is confirmed, the current strict selection criteria may be safely expanded so that more HCC patients could benefit from OLT and enjoy a prolonged life.
In conclusion, we show that HAb18G/CD147 can be a good drug target and Licartin is a promising new antimetastasis and recurrence agent for treating advanced HCC after OLT.作者: RichardTu 时间: 2009-7-2 23:33
