OBJECTIVE: To investigate the therapeutic effect and biological changes of hepatic arterial infusion of p53 gene by the percutaneous port catheter system on advanced hepatocellular carcinoma (HCC) through a prospective randomized trial. METHODS: A total of 48 patients with advanced HCC between May 2005 and January 2009 were divided into the treatment group (30) and the control group (18). The port catheter system was implanted through the right external iliac artery approach in all the cases; the target artery was determined according to the manifestation of the angiograph. The patients in the treatment group were given arterial infusion of p53 gene (Gendicine, Shenzhen Sibiono GeneTech Co, Ltd) with Gendicine (10vp) combined with hydroxycamptothecin (20 mg), once a week, for a course continuously for 3 weeks. The arterial infusion with hydroxycamptothecin (20 mg) was given to the patients in the control group. Pretreatment/posttreatment a fetus protein and Karnofsky Performance Status values, change of tumor according to Response Evaluation Criteria in Solid Tumors (RECIST), and the survival time were analyzed. Pretreatment/posttreatment expression of mutant p53 gene and spontaneous micronucleus formation in the peripheral blood were evaluated by flow cytometry and micronucleus test in vivo. RESULTS: The patients in the treatment group received 1 to 8 courses of treatment, in which the differences between pretreatment/posttreatment AFP and KPS values were significant (P < 0.05), whereas there was no significant difference (P > 0.05) between pretreatment/posttreatment AFP and KPS values within the control group. After 1 month, the survival rates of the treatment and control groups (96.6% and 94.4%, respectively) and changes in the tumor evaluated according to RECIST were significantly different (P < 0.05) between the 2 groups. After 3 months, the survival rates of the treatment and control groups (83.3% and 55.6%, respectively) and changes in the tumor were also significantly different between the 2 groups (P < 0.05). After 6 months, the survival rates (50% and 11%, respectively) and changes in the tumor were significantly different between the 2 groups (P < 0.05). After 9 months, the survival rates (23.3% and 0%, respectively) and changes in the tumor were significantly different between the 2 groups (P < 0.05). Finally, after 12 months, the survival rates (6.67% and 0%, respectively) and changes in the tumor were significantly different between the 2 groups (P < 0.05). The difference between the pretreatment and posttreatment mean rates of p53 expression in patients in the treatment group was very significant (P < 0.01). The difference between the posttreatment mean rates of the treatment group and the control group was also significant. CONCLUSIONS: Sequential therapy of p53 gene transcatheter arterial infusion was safe and could prolong the survival time of the patients. The biological study will play a positive role in guiding and monitoring the aspects of dosage selection and judgment of therapeutic efficacy.
RCT Entities:
OBJECTIVE: To investigate the therapeutic effect and biological changes of hepatic arterial infusion of p53 gene by the percutaneous port catheter system on advanced hepatocellular carcinoma (HCC) through a prospective randomized trial. METHODS: A total of 48 patients with advanced HCC between May 2005 and January 2009 were divided into the treatment group (30) and the control group (18). The port catheter system was implanted through the right external iliac artery approach in all the cases; the target artery was determined according to the manifestation of the angiograph. The patients in the treatment group were given arterial infusion of p53 gene (Gendicine, Shenzhen Sibiono GeneTech Co, Ltd) with Gendicine (10vp) combined with hydroxycamptothecin (20 mg), once a week, for a course continuously for 3 weeks. The arterial infusion with hydroxycamptothecin (20 mg) was given to the patients in the control group. Pretreatment/posttreatment a fetus protein and Karnofsky Performance Status values, change of tumor according to Response Evaluation Criteria in Solid Tumors (RECIST), and the survival time were analyzed. Pretreatment/posttreatment expression of mutant p53 gene and spontaneous micronucleus formation in the peripheral blood were evaluated by flow cytometry and micronucleus test in vivo. RESULTS: The patients in the treatment group received 1 to 8 courses of treatment, in which the differences between pretreatment/posttreatment AFP and KPS values were significant (P < 0.05), whereas there was no significant difference (P > 0.05) between pretreatment/posttreatment AFP and KPS values within the control group. After 1 month, the survival rates of the treatment and control groups (96.6% and 94.4%, respectively) and changes in the tumor evaluated according to RECIST were significantly different (P < 0.05) between the 2 groups. After 3 months, the survival rates of the treatment and control groups (83.3% and 55.6%, respectively) and changes in the tumor were also significantly different between the 2 groups (P < 0.05). After 6 months, the survival rates (50% and 11%, respectively) and changes in the tumor were significantly different between the 2 groups (P < 0.05). After 9 months, the survival rates (23.3% and 0%, respectively) and changes in the tumor were significantly different between the 2 groups (P < 0.05). Finally, after 12 months, the survival rates (6.67% and 0%, respectively) and changes in the tumor were significantly different between the 2 groups (P < 0.05). The difference between the pretreatment and posttreatment mean rates of p53 expression in patients in the treatment group was very significant (P < 0.01). The difference between the posttreatment mean rates of the treatment group and the control group was also significant. CONCLUSIONS: Sequential therapy of p53 gene transcatheter arterial infusion was safe and could prolong the survival time of the patients. The biological study will play a positive role in guiding and monitoring the aspects of dosage selection and judgment of therapeutic efficacy.