A clinical study evaluating dendritic and cytokine-induced killer cells combined with concurrent radiochemotherapy for stage IIIB non-small cell lung cancer

Non-small cell lung cancer: Adenocarcinoma

Non-small cell lung cancer: Adenocarcinoma

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Summary

The study aims to evaluate the efficacy of dendritic and cytokine-induced killer cells (DC-CIK) therapy combined with concurrent radiochemotherapy on patients with non-small lung cancer. The findings suggest that The combined therapy can improve the life quality and prolong the survival time of the patients.

Patients characteristics

63 patients with non-small cell lung cancer confirmed by histopathology that was not treated by chemotherapy; whose survival time was expected to be greater than three months; who were older than 18 years; who were generally fair; with Karnofsky performance score (KPS) higher than 70 points; with normal blood, liver and kidney functions; with no serious complications; with confirmed stage IIIB based on clinical manifestations, physical examination, computed tomography (CT), magnetic resonance imaging, and bone Emission Computed Tomography; and with lesions to be measured.

Methodology

Preparation of DC and CIK
Anticoagulated peripheral blood (100 mL) was collected from the patients. Mononuclear cells were isolated by Ficoll density gradient centrifugation and washed with 0.9% saline thrice. The cells were incubated for 2 hours at 37°C, under 5% CO2, 95% relative humidity using RPMI-1640 culture medium. Then the cell suspension was isolated and seeded in another culture flask. Interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor were added to the culture flasks of adherent cells immediately; tumor necrosis factor-alpha (TNF-α) was added on the 5th day. Interferon-gamma (IFN-γ) was added to the culture flasks of suspension cells immediately; IL-1, IL-2, and anti- CD3 mAb were added on the 2nd day. Culture medium was changed regularly. DC and CIK cells were co-cultured at a ratio of 1:10 on the 7th day using RPMI-1640 culture medium containing IL-2.
On the 12th day, DC and CIK cells were collected, washed, sub bagged, mixed with 5% human serum albumin, and intravenously administered for two or three transfusions.

Treatment

The chemotherapy regimen included the intravenous infusion of docetaxel [75 mg/ m2 on day 1 (D1)] and cisplatin (25 mg/m2 from D1-3), for a cycle of 21 days, for a total of four cycles as co-chemotherapy.For the radiotherapy regimen, all patients underwent three- dimensional conformal radiotherapy while undergoing concurrent chemotherapy; 5 mm CT was used to enhance the scan and simulator after fixing the membrane. Special attention was paid to reduce the dose in order to avoid threatening the lung, spinal cord, and heart. Radiation treatment required dose volume histogram assessment; for the whole lung, volume receiving at least 20 Gy (V20) was no more than 30%, for the spinal cord, the maximum dose was lower than 45 Gy, and for the heart, V40 was lower than 40%. Radiotherapy was prescribed at a dose of 200 cGy/ day, 5 times per week, at a tumor dose of approximately 60-70 Gy.
For DC-CIK immune cell therapy, in the two days prior to chemotherapy, blood was collected and cells were cultured in vitro for 12 days, and subsequently administered two or three times through intravenous transfusion. The regimen was a 21-day cycle, for a total four cycles.

Results

There was a significant difference in the RR, which was 83.3% in the study group, and 54.5% in the control group.Before treatment, the KPS in the study group was 75.0 ± 6.3 while it was 74.2 ± 6.1 in the control group. After treatment, the KPS in the study group was 78.7 ± 10.4, while it was 72.1 ± 10.5 in the control group.
Survival and follow-up
The patients’ detailed information, including addresses and telephone numbers, were recorded when admitted to hospital; 63 patients were followed up regularly for 12 months by telephone and outpatient services. 6-month overall survival of patients in researched group is 28 patients (93.3%) and 30 (90.9%) in control group. 1-year OS of the patients in researched group 25 (83.3% and 20 (60.6%).
Adverse reaction
Adverse effects mainly included leukopenia, gastrointestinal reactions, radiation pneumonitis, and radioactive esophagitis. Adverse effect of degrees I and II were common. No significant difference was observed between the two groups. One case was excluded from the control group for the leukopenia of degree IV. In the study group, 5 (16.7%) patients developed fever within 1-2 hour after the reinfusion of DC-CIK and underwent spontaneous defervescence.

Conclusion

The combination treatment with DC-CIK and concurrent radiotherapy and chemotherapy for the treatment of stage IIIB non-small cell lung cancer is better than radiotherapy and chemotherapy alone, and can improve quality of life, enhance immunity, and prolong survival.

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Scientific article publishing date :8/28/2015

Immucura identifier BSC21_224EN

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