| Background and ObjectiveNon-Hodgkin's lymphoma is a group of lymphoid malignancies with highly heterogeneity or diversity. Its incidence increased gradually in recent years. Diffuse Large B Cell Lymphoma (DLBCL) of NHL happened mostly in china. DLBCL is Intermediate grade lymphoma, mainly treated by chemistry. The chemotherapy programs we often used are the CHOP, BACOP, and so on. The complete remission rate of these chemotherapy programs is from 50% to 80% generally. Chemotherapy is the main method of comprehensive treatment to malignant lymphoma, but it is prone to recur and transfer, so the chemotherapy need more courses, more programs and repeated chemotherapy. Repeated chemotherapy can easily cause resistance to chemotherapy drug, and the resistance is the main reason for the failure of chemotherapy. Many researchers are trying to find some new drugs for malignant lymphoma to improve its efficacy, to prolong the rate of disease-free survival as much as possible and to improve the quality of life to patients in recent years.Thalidomide, also known as phthalate microphone pulse Ethers, was found as a drug with central inhibition during the development of antibiotics. It has some effect to sedation and hypnosis and initially used to treat nausea and vomiting for pregnant women. An Israeli doctor found that thalidomide had effects on the autoimmune symptoms of leprosy in 1965, so the drug was focused by people again. In 1998, the U.S. FDA approved the drug for the treatment for the erythema nodosum of leprosy. Further researches showed that thalidomide had effects on anti-angiogenesis and immunoregulatory, so it had effect on anti-tumor.Vascular endothelial growth factor (VEGF) is a functional glycoprotein with highly biological activity. Its main function is to vascular endothelial cells, it can promote split and generate chemotaxis of vascular endothelial cells, increase capillary permeability, thereby promoting proliferation and migration of endothelial cells, so VEGF makes a key role in angiogenesis of tumor. The researches show that VEGF is an important vascular growth facto. Patients with high expression of VEGF have low survival rates. This study was to observe the effect of angiogenesis inhibitors thalidomide combined with chemotherapy on the VEGF level in patient serum, so as to evaluate clinical significance of the combined treatment for non-Hodgkin's lymphoma.MethodsWe used ELISA kit to detect the concentration of VEGF in the serum in this study. Patients were randomly assigned by envelope method. Combined treatment groups:treated by thalidomide combined with chemotherapy; Chemotherapy groups: treated by CHOP. We treated 4 weeks as a cycle, we evaluated the treatment efficacy after 2 cycles. Refered to the standard of determine treatment efficacy of the WHO. We grouped according to changes in subjective symptoms before and after treatment and changes in the lesion observed by CT. Detected the absorbance value in 450nm wavelength by automatic computer microplate reader made by the Bio-Rad company in US. The concentration of VEGF was proportional to the absorbance. So that we could observe the effect of angiogenesis inhibitors thalidomide combined with chemotherapy on the VEGF level in patient serum, so as to evaluate clinical significance of the combined treatment for non-Hodgkin's lymphoma. Finally we analyzed the data by SPSS 13.0 statistical software.Results1. After two cycles of chemotherapy, all patients were reviewed by chest SCT, abdominal ultrasonography and comprehensive physical examination. There were no cases in progression. There were 7 cases of complete remission,5 cases of partial remission,8 patients with no change in chemotherapy groups, the efficiency was 60%. There were 12 cases of complete remission,4 cases of partial remission,4 patients with no change in combined treatment groups, the efficiency was 80%.2. There were no significant difference of VEGF levels in serum between the two groups before treatment (P>0.05). The VEGF levels in serum were not significant decreased after treatment in the chemotherapy groups and there were not more differences of VEGF levels in serum between before chemotherapy and after chemotherapy (P>0.05). The VEGF levels in serum decreased after treatment in the combined treatment groups and there were more differences of VEGF levels in serum between before treatment and after treatment (P<0.05). There were more difference of VEGF levels in serum between the two groups after treatment (P<0.05).There were more differences of VEGF levels in serum between two groups before treatment and healthy groups(P<0.05). The VEGF levels in serum increased after treatment to patients with no change.3. Safety Assessment1) Hematological adverse reactionsHematological adverse reactions were mainly for different levels of leucopenia, neutropenia, thrombocytopenia and anemia. Most wasⅠ°～Ⅱ°marrow suppression.8 patients (20%) appearedⅢ°～IV°marrow suppression, another 8 patients appeared neutropenia and were gradeⅣ(<0.5×109/L),4 patients appeared thrombocytopenia and were gradeⅢ(<50×109).5 patients appeared anemia,3 of them were gradeⅡ(Hb 80g/L～94g/L),2 of them were gradeⅢ(Hb 65g/L～79g/L).Most of the hematological adverse reactions could be corrected by application of hematopoietic cell-stimulating factor and adding raw materials and other measures.2) Non-hematological adverse reactionsAbout 80% of the patients appeared non-hematological adverse reactions, but the reactions was slight, majority of them could be tolerated and did not affect the treatment. Adverse reactions of gradeⅢ-Ⅳwere rare, only 3 cases appeared gradeⅢgastrointestinal reactions and were relief after the therapy of enhanced antiemetic drugs and rehydration. Non-hematological adverse reactions are shown in the table.Conclusion1. The expression of VEGF in malignant lymphoma was significantly higher than in healthy controls, which suggest that VEGF involved in the occurrence and development of malignant lymphoma. This may provide a theoretical basis for the early clinical diagnosis of malignant lymphoma.2. The thalidomide could more decrease the VEGF levels in serum in the non-Hodgkin's lymphoma and had effects on anti-angiogenesis, so it had effect on anti-tumor.3. The thalidomide combined with chemotherapy program CHOP treatment for non-Hodgkin's lymphoma could achieve high efficiency.4. Most of the adverse reactions of the thalidomide combined with CHOP chemotherapy were mild, most patients could tolerate and had higher quality of life. |
PDF Full Text Request