Combined Treatment with Autologous CIK Cells, Radiotherapy and Chemotherapy in Advanced Cervical Cancer

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Summary

The goal of this study is to see how effective autologous cytokine induced killer (CIK) cells paired with radiochemotherapy are in treating advanced cervical cancer. The findings imply that autologous CIK cells transfusion combined with radiochemotherapy has a superior short-term efficacy than radiochemotherapy alone in the treatment of advanced cervical cancer, with minimal side effects.

Patients characteristics

Total 89 cases of cervical cancer patients ages 36-80 years old with median age of 54 years old were observed in this study, including squamous cell carcinoma in 77 cases, adenocarcinoma in 8 cases, and other (small cell carcinoma and adenosquamous carcinoma) 4 cases. Clinical staging was performed according to the International Federation of Gynecology and Obstetrics (FIGO) criteria: Stage II A-II B 34 cases, Stage III A-III B 46 cases, Stage IV 9 cases. Karnofsky (KPS) score was more than 70 points. Liver function, kidney function and blood routine were normal without serious heart, liver or kidney diseases. The predicted survival time was more than 3 months.

Methodology

CIK cell preparations
Mononuclear cells were isolated from autologous peripheral blood using a Ficoll method. Then they were washed with RPMI 1640 three times and suspended in RPMI 1640 complete medium at a cell density of 2 × 106 /mL.
Transfusion 1 time per day with total 4 days as a course. Peripheral blood was collected on the day before the first chemotherapy (4 weeks post-radiotherapy) in the CIK treatment group to isolate and culture CIK cells. After 14 days of culture, CIK cells transfusion was performed, and the second chemotherapy was carried out one week after the course. Second collection of peripheral blood was performed on the day before the second chemotherapy. Chemotherapy alternates with CIK cells transfusion for totally 4 ~ 6 courses in CIK treatment group.

Treatment

Radiotherapy and chemotherapy
The chemotherapy regimen used in the two groups was paclitaxel or gemcitabine combined with cisplatin, every 28 days for one cycle. Conformal radiotherapy combined with intracavitary brachytherapy was used in the radiotherapy process. The first dose of patients with radical radiotherapy was whole pelvic irradiation 30 ~ 36 Gy, four fields box of types 20 Gy, combined with intracavitary irradiation 30 ~ 38 Gy, with a dose of 70~76 Gy at point A and 50 ~ 56 Gy at point B. The radiation dose in patients with pelvic recurrence was GTV 60 ~ 66 Gy. Patients were treated simultaneously with radiotherapy and combination chemotherapy.

Results

Short-Term Therapeutic Efficacy
The effective rate 1 month post-treatment of the CIK treatment group was 88.64% (39/44), while in the control group it was 68.89% (31/45).Immune Function
In the CIK treatment group, the levels of T lymphocyte subsets CD3+ and CD4+/CD8+ ratio were significantly increased on day T25 compared with day T14. The levels of CD3+, CD4+ and CD4+/CD8+ ratio was slightly decreased on day T14 compared with day B1.
In the control group, the levels of CD3+, CD4+ and CD4+/CD8+ ratio were increased, while CD8+ level was decreased on day T25 compared with day T14.
Adverse reaction
At the end of CIK cells transfusion, blood routine, liver and kidney function results of all the patients were not significantly changed. The most common adverse reaction was transient hypothermia (15 patients, body temperature ≤ 38. 5 °C) after CIK cells transfusion. It was turned to normal within 24 hours without high fever recurrence.
Karnofsky Performance Score (KPS)
Before starting the treatment, there was no significant difference between the CIK group and the control group. After the treatment, the KPS score of the CIK group was 0 ~ 20 points higher before treatment, which has significant difference compared with the control group. In addition, there was significant difference of KPS score both in the CIK and the control group after treatment. These data revealed that the quality of life was improved in both groups after treatment, and the improvement in the autologous CIK cells treatment group was more obvious.
Survival rates
All patients were followed up by telephone review. The follow-up time was 10 ~ 38 months, and the follow- up rate was 100%. The 1-, 2- and 3-year survival rates in the treatment group (93.18%, 77.27% and 47.73%) were higher than those in the control group (88.88%, 68.89% and 42.22%), although no significant differences were observed.

Conclusion

In conclusion, these results indicate that autologous CIK cells transfusion combined with chemoradiation therapy was confirmed to be an ideal treatment of advanced cervical cancer with the advantage of higher short-term therapeutic efficacy, improve of immune function and life quality with low side effects.

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Scientific article publishing date 12/3/2018

Immucura identifier BSC21_273EN

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