Research Of Clinical Effection Of Deddritic Cells Therapy Combined With Intravesical Perfusion Of Epirubicin On Bladder Cancer After TURBT

Background In China, bladder cancer is the most common malignant tumor in urinary system, with a lower grade but a higher recurrence rate. To prevent the recurrence of bladder cancer, patients with superficial bladder cancer or T2a invasive bladder cancer often receive a routine intravesical infusion therapy after transurethral resection of bladder tumor (TURBT). However, almost all the infusion therapy drugs, including BCG and all kinds of chemotherapeutic agents such as mitomycin C, pirarubicin and epirubicin (EPI), have some unresolvable problems, for example, uncertain long-term efficacy, high incidence of side effects and even some serious complication. Recent studies have shown that dendritic cells (DC) immune therapy has achieved good results in a variety of anti-cancer experiments, and brought new hope for the cancer patients. Chemotherapy combined with immune therapy can stimulate and regulate non-specific immune of the body, by this it not only can improve the long-term efficacy, but also can avoid the toxic side effects resulting from heavy dosage of chemotherapeutic agents.Objective To assess the influence of DC therapy combined with intravesical perfusion of EPI on 2 years recurrence rate of bladder cancer. Observe the adverse reaction in patients after DC therapy combined with intravesical perfusion of EPI.Make clear the changes of CD3+, CD4+, CD8+ and CD4+/CD8±levels in peripheral blood of the patients who have received DC therapy and explore the immune mechanism of DC anti-tumor therapeuty.Methods Select 168 bladder cancer patients who received TURBT in our hospital from January 2005 to August 2008. All the tumors were resected completely including the tissues 2cm away from the tumor and all the pathological examinations showed no cancer cells on the edge of the tumor. The patients were randomly divided into three groups. Group A (DC combination therapy group) were given the first intravesical infusion of EPI (30mg EPI dissolved in 50mL saline) within the first week after TURBT, changing body position (supine, prone, left lateral and right lateral position) every 30min after infusion and discharge the perfusate after 2h. One time per week for six times, then one time every two weeks for six times, finally one time every month for 19 months. During the above chemotherapy course, all members in Group A also received intradermal injection of 106~107 DC on the groin area at the 3th,4th,6th,7th week after TURBT. This was the first course of DC treatment and the patients in Group A received their second course of DC treatment from the 27th week after TURBT, which was the same as the first one. Group B (EPI infusion group) were treated only with EPI bladder perfusion after TURBT, the infusion method was same with Group A. Group C (BCG infusion group) were treated only with BCG bladder perfusion after TURBT, the infusion method was same with EPI bladder perfusion. All patients in three groups were followed up for 2 years to observe and compare the tumor recurrence rate, adverse reactions and the influence of DC on T lymphocyte subsets.Results The two-year recurrence rates of three groups were 10%,25.8% and 11.3% respectively, the difference between Group C and Group B as well as the difference between Group A and Group B was statistically significant (P<0.05), while the difference between Group A and Group C was not statistically significant (P>0.05). The adverse reaction rates of three groups were 20%,10.6% and 40.3% respectively, the difference between Group B and Group C as well as the difference between Group A and Group C was statistically significant(P<0.05),while the difference between Group A and Group B was not statistically significant (P>0.05). The peripheral blood CD3, CD4and CD4/CD8 ratio of Group A increased after DC treatment, the differences were significant compared with those before DC treatment(P<0.05), the differences were also statistically significant compared with the Group B at the same time(P <0.05).Conclusion Compared with EPI infusion group, DC therapy combined with intravesical perfusion of EPI can effectively reduce two-year recurrence rate of bladder cancer. The anti-tumor effect is similar with BCG infusion group while the adverse reaction rate was far below BCG infusion group. DC vaccination can increase peripheral blood CD3, CD4 and CD4/CD8 ratio so as to improve the patients'body immunity in short time. Therefore, DC immune therapy combined with intravesical chemotherapy provides a new way for the adjuvant treatment of bladder cancer.