| ObjectiveThe aim of the present study is to evaluate the efficacy and safety of Chinese Herbal Medicine (CHM) modified XIAOJI decoction(MXJD) combines with cytokine induced killer cells and epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI) erlotinib in the treatment of advanced non-small cell lung cancer(NSCLC). To explore a new treating mode and provide a new evidence-based medical evidences by CHM MXJD combination of adoptive immunotherapy and molecular targeted therapy in the treatment of NSCLC.MethodsIn this prospective, randomly, controlled and monocentric clinical trial. Participants were divided into treatment group (A) and control group (B) according to the inclusive criteria. Group A was placed on CHM MXJD (150 ml, bid, po)+Cytokine induced killer cells [(1-3) x 109/time, qd, ivd, d1-3]+ Erlotinib (150 mg qd, po),30 days/cycle, at least 3 consecutive cycles of treatment, while group B took CHM MXJD and Erlotinib only. The clinical characteristics of all participants would getting a baseline evaluation. Progression free survival (PFS) was defined as the primary endpoint, while the secondary endpoint was including objective response rate (ORR), disease control rate(DCR), one-year survival rate, quality of life(QOL), toxicity and immune function evaluation. Karnofsky performance score(KPS), lung cancer related symptom scores(LCRSS) in Traditional Chinese medicine (TCM) and lung cancer symptom scale (LCSS) were performed to the evaluation of the QOL. General physical function and the common adverse events (AEs) were adopted to evaluate the toxicity and security.ResultsParticipants were admitted in the Department of Medical Oncology of Guangdong Provincial Hospital of Chinese Medicine from October 2013 to October 2015.5 cases were dropped out until follow-up to March 1,2016. Of 61 patients were incorporated into the study and randomly divided into group A(30) and group B(31).There was no statistical difference between the two groups in clinical characteristics (P>0.05).1. Primary endpointOutcomes indicated that the FPS of all lines in the group A was significant longer than the group B, it was 16.09 months (95%CI 13.41-18.77) vs.10.85 months (95%CI 8.51-13.18) and demonstrated significant statistical difference (P= 0.008, HR=0.456,95%CI 0.26-0.83).2. Secondary endpoints(1) ORR and DCR. The group A was superior to the group B (43.3%vs.22.6% and 100%vs.90.3%), but there was no significant difference (P>0.05). Further stratified analysis showed that the ORR with significant difference in targeted therapy choice (P=0.019), but found no statistical difference in aspect of smoking status, pathological types, status of EGFR gene and syndrome differentiation in TCMCP>0.05). Two groups DCR in smoking index and EGFR status and the targeted therapy line were proved statistical differences (P=0.032, P=0.040, P=0.003, respectively).(2) One-year survival rate. One-year survival rate compared between the two groups were 83.83%vs.80.60%. Group A was slightly higher than group B, while no significant difference was observed(P>0.05).(3)QOL. Referring to the improved and the effective grade, group A are superior to the group B(30%vs.22.6%,56.7%vs.54.8%), but found no statistical difference(P=0.064). The LCRSS in TCM had a certain degree reduction in the contrast of the two groups before and after the treatment. Group A(89.97 vs.70.87) was more obvious compared with group B(85.68 vs. 69.65), and statistical test showed statistical significance(P<0.0001). The LCSS score declined in actual degree after the treatment. Group A(57.70 vs. 47.33) reduced fractional was obviously compared with the group B(56.74 vs. 46.90), and there was statistical significance(p<0.0001).(4)Toxicity and security evaluation. Studies indicated that the toxicity of the group A was less frequent and milder than the group B.The incidence rate of rash and diarrhea was 56.7%vs.61.3%and 26.6%vs.41.9%, respectively(P>0.05). Skin toxicity serious than grade III occurred rate was 3.33%vs.9.68%in the two groups (P>0.05). Long-term safety assessment showed the hematological toxicity can be effectively improved. In additional, both of the two groups decreased significantly in rash, diarrhea incidence compared with the previous period, and with no more damage to the hepatic and renal function. What is more important, there were no serious adverse events and related deaths during the follow-up period.(5) Immune index. The T lymphocytes subsets in the two groups were evaluated before and during the adjuvant targeted therapy or immunotherapy. Compared with before and after treatment, both groups T lymphocyte subsets like CD3+T, CD3+CD4T, CD16+CD56+NK percentage and CD3+CD4/CD3+CD8 ratio are somewhat elevated. But only group A reached statistical significance difference (P< 0.05). Referring to the CD3+CD8T cell percentage, statistically significant only found in the group A(P< 0.05). While there was no statistical significance in the percentage change of CD19+B cells neither group A nor group B(P>0.05).Conclusion1. Chinese herbal compound MXJD combined with cytokine induced killer cells adoptive cellular immunotherapy and erlotinib molecular targeted therapy can effectively prolong the PFS and improve ORR, DCR, one year survival rate in advanced NSCLC.2. The small molecules targeted therapy with CHM combined plus immunotherapy in advanced NSCLC can reduce the common adverse reactions effectively, with nice tolerability and safety. Meanwhile, it can improve the symptoms, the immune function and QOF of patients in advanced NSCLC. |
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