Phase I safety and pharmacokinetic study of bevacizumab in Chinese patients with advanced cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>bevacizumab is a humanized recombinant vascular endothelial growth factor (VEGF) monoclonal antibody, which specifically binds to VEGF and inhibits tumor cell growth, proliferation and metastasis. We aimed to investigate the safety and pharmacokinetics of bevacizumab in Chinese patients with advanced cancer.</p><p><b>METHODS</b>Thirty-nine Chinese patients with metastatic or relapsed cancers who failed prior therapy were enrolled in this phase I study of bevacizumab. Bevacizumab was infused by a calculated pump at doses from 5 mg/kg to 15 mg/kg in 90 minutes. Patients underwent serial pharmacokinetic evaluations. Patients that received at least one infusion of bevacizumab were included in the safety study.</p><p><b>RESULTS</b>Thirty-five patients finished all 5 infusions following protocol. One patient withdrew after 3 infusions due to grade 3 proteinuria. Common adverse events possibly related to the study drug were proteinuria (17/39, 43.6%), hypertension (13/39, 33.3%), gingival bleeding (7/39, 17.9%), epistaxis (6/39, 15.4%), pharyngeal inflammation (6/39, 15.4%), fatigue (6/39, 15.4%) and stomatitis (4/39, 10.3%). Bevacizumab pharmacokinetics was linear within the range of 5 mg/kg q2w--10 mg/kg q2w and 15 mg/kg q3w. CL (clearance), Vd (volume of distribution at elimination) and Vss (volume of distribution at steady state) were similar after single and multiple doses at 5, 10 and 15 mg/kg.</p><p><b>CONCLUSIONS</b>Bevacizumab is well tolerated in Chinese patients. No unexpected adverse events were observed. There is no racial difference in the pharmacokinetics.</p>

Efficacy and safety of bevacizumab plus capecitabine for metastatic colorectal cancer / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of bevacizumab plus capecitabine in treating metastatic colorectal cancer(mCRC).</p><p><b>METHODS</b>Eleven patients with mCRC (6 females and 5 males) were enrolled in this study. Bevacizumab was given with 5 mg/kg every two weeks in five patients, 10 mg/kg every two weeks in four patients and 15 mg/kg every three weeks in two patients. All patients received capecitabine 2000 mg/m2 per day for 14 days.</p><p><b>RESULTS</b>Five of 11 patients had partial response and five patients had stable disease and two patients had progressive disease. The disease control rate was 90.9%. The progress-free survival were 4 months and the median overall survival time were 15 months. The adverse events related to bevacizumab were grade 2 hypertension in 3 patients (27.3%) and grade 1 or 2 proteinuria in 4 patients (36.4%). Other adverse events such as mucositis, fatigue, subcutaneous haemorrhage were also observed. No thromboembolism or severe haemorrhage happened. No other grade 3 or 4 adverse events were observed.The adverse events in the combined therapy were hand-foot-syndrome (54.6%), diarrhea (27.3%), and neutropenia (18.2%), mainly due to capecitabine.</p><p><b>CONCLUSIONS</b>The combination of bevacizumab plus capecitabine has definite benefit in patients with mCRC. However,these benefits can not be maintained after the withdrawal of bevacizumab. The adverse drug reactions are well tolerated.</p>

Feasibility of erlotinib after gefitinib failure in patients with advanced pulmonary adenocarcinoma previously responding to gefitinib / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the efficacy and progression-free survival of erlotinib after progression of disease to gefitinib in patients with advanced pulmonary adenocarcinoma who previously obtained a disease control with gefitinib.</p><p><b>METHOD</b>In this retrospective study, 12 patients with advanced or metastatic pulmonary adenocarcinoma,who were previously obtained a partial response or a stable disease with gefitinib,were treated with erlotinib after gefitinib failure. Erlotinib efficiency, progression-free survival and overall survival were analyzed.</p><p><b>RESULTS</b>Nice (75%)achieved stable disease and three (25%) achieved progression disease with erlotinib treatment after gefitinib failure. No complete response or partial response was observed. The disease control rate was 75%. The median progression-free survival and overall survival of erlotinib were 180 days and 831 days.</p><p><b>CONCLUSION</b>Erlotinib seems to be an optional treatment after gefitinib failure for advanced pulmonary adenocarcinoma patients,who previously responded to gefitinib.</p>

Effects of exercises training on the rats aorta stress and expression of NF-kappaB and c-Fos / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effect of different intensity exercise training on the rat aorta stress and expression of NF-kappaB and c-Fos.</p><p><b>METHODS</b>We used treadmill exercise to establish the rat models of aerobic exercise and fatigue exercise, applied immunohistochemistry of SABC to measure the effect of different intensity exercise training on expression of NF-kappaB and c-Fos in the VEC and VSMC of rat aorta.</p><p><b>RESULTS</b>The change of aorta blood pressure, compared with the control group, which had significant increase in both aerobic exercise and fatigue exercise (P < 0.05), but there had no remarkable difference between inaerobic exercise and fatigue exercise. Compared with the control group, the expression of NF-kappaB and c-Fos of VEC and VSMC in aerobic exercise rats remarkably reduced, the opening angle increased remarkably (P < 0.05), and the expression of NF-kappaB and c-Fos of VEC and VSMC in fatigue exercise rats distinguished upregulated (P < 0.05). Compared with the aerobic training group, there was distinguished difference in both the expression of NF-kappaB and c-Fos of VEC and VSMC and the opening angle of pectoralis aorta in fatigue training rats (P < 0.05). This indicated that different intensity training had different effect on the expression of NF-kappaB and c-Fos of VEC and VSMC of rat aorta, and the increase trend of expression of fatigue training group was more remarkably.</p><p><b>CONCLUSION</b>Expression change of NF-kappaB and c-Fos of VEC and VSMC of rat aorta was caused by exercise training, and which had a closed relation with the exercise intensity. Chronic shear stress of aerobic training made the expression of NF-kappaB and c-Fos of VEC and VSMC of aorta distinguished downregulated, which had relationship with homeostasis that VEC and VSMC maintained the blood vessel function. Fatigue training caused the increase of wall frictional shear stress and circumferential stresses, excessive shear stress caused the expression of NF-kappaB and c-Fos of VEC and VSMC of aorta significant upregulated, blood vessel happened non-unequal growth exists, and resulted in the remodeling of structure and function of blood vessel.</p>