| Objective To evaluate the safety and efficacy of endostatin (rh-endostatin, YH-16) combined with docetaxel and carboplatin (TP)regimen for the adjuvant treatment of non-small lung cancer (NSCLC) and its impact on circulating blood markers.Methods 36 patients with stage Ib-IIIa 4 weeks after radical resection of NSCLC, were randomly divided into the treatment group, endostatin plus TP regimen, and the control group, TP regimen only, respectively, for 4 cycles. The postoperative security of human recombination endostatin was observed by comparing of the adverse reactions, especially by the postoperative tissue healing. The relationships between the levels of biomarkers Ki-67, microvessel density (MVD) of CD34 and VEGF and the efficacy were studied. Ki67 labeling index:3 high power fields in each section were selected, and 100 tumor cells were counted in each high power field, labeling index of each field of vision=the number of positive cells/100×100%, and the labeling index was the average percents of each section.CD34 the areas of vascular lumen larger than 8 red blood cells or_larger blood of smooth muscle around were not included in count the areas of microvessel density were selected in low power field (hotspot),and counted in 400 times magnification. The mean of the five visual fields as MVD AB value method of VEGF:A: staining intensity of positive cells:0 point= no stain,1 point= slight stain,2 points= brown stan,3 points= dark brown stain. B:the ratio of positive cells(the number of positive cell/the number of tumor cells):1 point=the ratio≤10%,2 points=the ratio≤75%,3 points=the ratio>75%. The patients made chest CT scan and abdominal B ultrasound once a month in recent clinical assessment and the numbers of peripheral circulating Endothelial Cells and the levels of tumor marker CEA, NSE and CYFR21-1 before and after operation were measured. Results The positive expression rate of Ki-67 was 52.7%(19/36),and the positive cells of Ki-67 with squamous cell carcinoma was more than with adenocarcinoma, (p<0.01). The positive group in two years survival rate was lower than the negative group. The positive expression rate of VEGF was 66.7%(24/36), and the positive group one and two years survival rate were higher than the control group, the positive cases of two years survival rate was lower than the negative group, however, no significant. CD34 actual range is 4 to 56 bands.MVD was related to stage, p<0.05. The numbers of CEC and the levels of CEA, NSE and CYFR21-1 decreased after treatment. There were significant differences in CEC between treatment group and control group after four cycles of treatment, the numbers of CEC of 5 patients with recurrence or metastasis increased from 3.25±1.24/105 to 20.86±0.26/105, and decreased to 0.95±0.32/105 after treatment.31 patients in the same period with no recurrence or metastasis the CEC number decreased from 3.11±1.75/105 to 0.87±0.32/105, respectively(p = 0.016). Disease-free survival time (DFS) was longer in treatment group than control group and had significant difference. CEC was significantly increased in recurrent and metastasis cases and decreased after effective treatment. NSE in the treatment group and in the control group after four cycles treatment were 9.97±1.85和12.96±1.39 respectively, and was significant difference between them (P= 0.013).There was not significantly difference in postoperative complications in two groups, there was no bronchial margin and wound disunion occurred. Endostatin adverse reactions were mild, mainly cardiac complications. One years survival rate of treatment group and control group were 100% and 94.4%, two years survival rate were 88.9% and 77.8%. The Long-term efficacy remains to be studied.Conclusion Patients with positive VEGF got better efficacy from endostatin treatment. The levels of CD34 and VEGF have positive correlations. Four weeks after operation, endostatin did not show any influence on wound healing. The effect endostatin combined with TP seem to be superior to TP alone in some short term index for the treatment of postoperative NSCLC even though long-term survival is still anticipated. CEC, as a biomarker, may be useful in predicting the efficacy of the synergistic treatment. |
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