| Objective: To observe the efficacy and security of recombinant human endostatin combined with cisplatin in the treatment of patients with advanced malignant tumor associated with malignant pleural effusion. A preliminary study of the relationship between the VEGF concentration of pleural effusion and the short-term efficacy of recombinant human endostatin combined with cisplatin in the treatment of malignant pleural effusion patients, and the relationship between the VEGF concentration of pleural effusion and progression free survival time of patients.Methods: 36 cases of advanced malignant tumor patients who accompanied with malignant pleural effusion were randomly divided into recombinant human endostatin combined with cisplatin group and single drug cisplatin group. All of the patients were treated with pleural infusion therapy. Before treatment, all patients were examined by ultrasonography, the operation of thoracentesis drainage catheter were did in the aseptic environment, and adequate drainaged pleural effusion of the patients. When the pleural effusion was drained, given the drugs injected into the thoracic cavity. 5ml pleural effusion of the patients were collected before and after treatment. Pleural effusion of the patients that were collected immediately placed-20℃ refrigerator preservation. There were 19 patients in the combined group, who were injected Endostar 45-60 mg and Cisplatin 50 mg in thoracic cavity; There were 17 patients in the Cisplatin group, who were injected Cisplatin 50 mg in thoracic cavity,1 week 2 times, every 2 weeks for 1 cycles. After perfusion given the patients dexamethasone 5mg to reduce toxicity, and the patients were asked to over and over again for 15 minutes. All patients must complete 1 cycles of treatment or more. The term efficacy of patients were evaluated according to standard for evaluating the efficacy of malignant pleural effusion by WHO, the adverse drug reactions of patients were evaluated by AE3.0 NCI-CTC classification criteria. The progression free survival time and patients’ quality of life were evaluated also, and the patients’ quality of life improvement were evaluated by KPS score changes before and after treatment. The concentration of vascular endothelial growth factor(VEGF) in pleural effusion was detected by double antibody sandwich enzyme-linked immunosorbent assay(ELISA) before and after treatment. The SPSS16.0 statistical software package were used to analysis of the data. The measurement data were recorded by mean plus or minus standard deviation and compared by t test. The counting data compared by chi square test. The homogeneity of variance of VEGF concentration was analyzed by F test. Survival analysis was carried out using Kaplan-Meier method. All the results were statistically significant in P < 0.05.Results: Comparison of the short term efficacy of the two groups, the combination group CR 5 cases, PR 9 cases, the effective rate was 73.6%; in the cisplatin group CR 2 cases, PR 5 cases, the effective rate(RR) was 41.1%, Chi square test χ2=3.901, P=0.048, the difference was statistically significant. In 36 patients, the median PFS were 4.6 months; the median PFS of the two groups were 4.4 months and 4.9 months respectively(χ2=5.943, P=0.015), The comparison between the two groups, P < 0.05, the difference was statistically significant. The improvement of the quality of life of the patients, 12 cases were improved, 4 cases were stable, 4 cases were deteriorated, and the improvement rate was 63.1% in the combined group;10 cases were improved, 5 cases were stable, 2 cases were worse, and the improvement rate was 58.8% in the cisplatin group. Chi square test χ2=0.071, P=0.790, the difference was not statistically significant. During the treatment, the two groups of patients with toxicity were mainly fever, chest pain, nausea and vomiting, bone marrow suppression, all of that were the second degree of toxicity, there was no treatment related death occurred. In the combined group, there were 5 cases of fever, 6 cases of chest pain, 6 cases of nausea and vomiting, and 5 cases of bone marrow suppression. In the cisplatin group, there were 4 cases of fever, 4 cases of chest pain, 7 cases of nausea and vomiting, 5 cases of bone marrow suppression. In the two groups, the values of P were all greater than 0.05, with no significant difference. Before treatment, pleural effusion VEGF concentrations were 488.28 + 97.13pg/ml and 451.07 + 100.54pg/ml respectively. The comparison between the two groups, P=0.204 P t=1.289 > 0.05, the difference was not statistically significant. After treatment the concentration of VEGF in combined group was 239.85 + 72.03pg/ml, which was significantly lower than before treatment, T=9.852, P < 0.001;the concentration of VEGF in the cisplatin group was 298.86 + 82.73pg/ml, which was lower than that before treatment, t=5.727, P < 0.001, the difference were statistically significant. The average descent value of VEGF concentration in the combined group and the cisplatin group were 246.45 + 57.73pg/ml and 152.21 + 53.71pg/ml respectively. The reduction value of the combined group was significantly higher than that of the cisplatin group, t=5.797 P < 0.001,the difference was statistically significant. The curative effect of 36 cases was effective(CR+PR) there were 21 cases; the invalid group(SD+PD) had 15 cases. The average descent values of VEGF concentrations were 256.43 + pg/ml, 120.83 + 24.62 49.57pg/ml, respectively. The comparison between the two groups, t=9.741, P < 0.001, the difference was statistically significant. Univariate analysis of the VEGF concentration of patients with malignant pleural effusion before treatment was not an independent prognostic factor for patients of PFS.Conclusion: The recombinant human endostatin combined with cisplatin in the treatment of malignant pleural effusion could further inhibiting the biological effects of VEGF that improve efficacy compared with single-agent cisplatin and prolong the progression free survival time of the patients. It also can improve the quality of life of the patients, that does not increase the patient, and the patients ’ tolerance is good. |
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