贝伐单抗联合肝动脉化疗栓塞术对36例晚期原发性肝癌生存预后的影响分析

目的：探讨贝伐单抗联合肝动脉化疗栓塞术（TACE）治疗晚期原发性肝癌的临床疗效及对生存预后的影响。方法：72例晚期原发性肝癌患者随机分为对照组和观察组各36例。对照组给予TACE治疗,观察组则给予动脉灌注贝伐单抗联合TACE治疗。比较两组患者的临床疗效、不良反应、卡氏生存质量评分以及6、12个月生存率及治疗前后血清甲胎蛋白（AFP）和癌胚抗原（CEA）的水平。结果：观察组治疗后的总有效率（16.67%）和临床获益率（77.78%）显著高于对照组的5.56%和55.56%（P＜0.05）;观察组患者治疗后血清AFP（416.52±10.89）mg/L和CEA（254.57±50.72） mg/L水平显著低于对照组的（468.34±11.89）mg/L和（314.56±69.84）mg/L（P＜0.05）。观察组治疗后的KPS评分（76.86±6.75）分,显著高于对照组的（72.79±5.83）分（P＜0.05）;观察组治疗后6个月的生存率为91.67%,高于对照组的86.11%（P＞0.05）。观察组治疗后12个月的生存率为83.33%,显著高于对照组的61.11%（P＜0.05）;两组患者发热、腹痛、黑便、过敏反应和转氨酶升高等不良反应的发生率均无统计学意义。结论：贝伐单抗联合TACE治疗晚期原发性肝癌可提高患者的生存质量,延长患者的生存时间,降低患者血清AFP和CEA的水平,疗效确切,值得应用于临床。     

Cancer du sein triple-négatif : caractéristiques histocliniques et moléculaires,prise en charge et perspectives thérapeutiques

Triple-negative breast cancer (TNBC), as defined by the absence of estrogen and progesterone receptor expression, as well as the lack of HER2 overexpression/amplification, corresponds to 15% of breast cancer and represents an aggressive form of the disease. TNBC are frequently confounded with basal subtype in the molecular classification of breast cancer and also share some similarities with BRCA1-mutated tumors. Epidemiological and clinical characteristics are distinct from other subtypes, including a younger age at diagnosis, a higher risk of relapse in spite of increased chemosensitivity, and a higher incidence of lung and brain metastatic relapses. Conventional cytotoxics remain the mainstay of current systemic management but recent evaluation of more targeted therapeutics, including specific cytotoxics (such as the use of platinum salts), PARP and EGFR inhibition, and antiangiogenics have been performed, providing contrasted but rather disappointing results. Recent data indicate that TNBC represent a heterogeneous entity composed of multiple and distinct molecular subtypes, which should deserve specific targeted therapeutics.     

Intravitreal tissue plasminogen activator for treatment of vitreomacular adhesion

AIM: To evaluate the role of a single intravitreal injection of tissue plasminogen activator alone (TPA) for treatment of vitreomacular traction and the effect of combined intravitreal TPA and bevacizumab on retinal vascular diseases. METHODS: In this prospective, interventional case series a total of 24 eyes from 24 patients were studied. There were 5 eyes with symptomatic vitreomacular traction syndrome (VMT) and 19 eyes with retinal vascular diseases including diabetic macular edema (DME), diabetic vitreous hemorrhage (VH), central retinal vein occlusion (CRVO) and neovascular age related macular degeneration (AMD). Measurement of visual acuity, B-scan and OCT were performed at the baseline and 1mo after injections. Three eyes with VMT received a single intravitreal injection of 50 μg and two eyes received 100 μg TPA. Totally 19 eyes with retinal vascular diseases received combined intravitreal TPA (50 μg) and Bevacizumab (1.25 mg). RESULTS: The mean ages for retinal vascular diseases and VMT patients were 56.8y and 60.4y, respectively. Ten patients (41.7%) were male and 14 patients (58.3%) were female. 22 eyes (91.7%) were phakic and 2 eyes (8.3%) were pseudophakic. The incidence of posterior vitreous detachment (PVD) was 0% (0 of 5) and 57.8% (11 of 19) for VMT and retinal vascular diseases, respectively (P=0.04). Improvement of best corrected visual acuity (BCVA) and decrement of central macular thickness (CMT) were significantly greater in PVD positive eyes compared with PVD negative eyes. CONCLUSION: Intravitreal injection of TPA was not successful to induce complete PVD in VMT patients. Combined intravitreal injection of TPA and Bevacizumab can induce PVD and improve BCVA and decrease central macular thickness in eyes with retinal vascular diseases.     

Foveal thickness reduction after anti-vascular endothelial growth factor treatment in chronic diabetic macular edema

AIM: To report foveal thickness reduction in eyes with resolution of macular edema and recovery of a foveal depression after one-year of anti-vascular endothelial growth factor (anti-VEGF) therapy for center-involving diabetic macular edema (DME). METHODS: Foveal thickness was assessed with optical coherence tomography to determine the central subfield foveal thickness (CSFT) and macular volume in 42 eyes with DME (CSFT>275 µm). Evaluations also included measurement of best-corrected visual acuity (BCVA), and were performed at baseline, and upon foveal depression recovery achieved after 12 monthly intravitreal injections of either 1.5 mg/0.06 mL bevacizumab (n=21) or 0.5 mg/0.05 mL ranibizumab (n=21). Data was compared to 42 eyes of normally sighted, non-diabetic, healthy individuals with similar age, gender and race distributions. RESULTS: Mean baseline BCVA was 0.59±0.04 and 0.32± 0.03 logMAR (P<0.001) after treatment and resolution of DME, with all, but 3 eyes, showing BCVA improvement. Mean CSFT before treatment was 422.0±20.0 µm, and after treatment, decreased to 241.6±4.6 µm (P<0.001), which is significantly thinner than CSFT found in control subjects (272.0±3.4 µm; P<0.001). Moreover, in 33/42 DM eyes (79%), CSTF was thinner than the matched control eye. Macular volume showed comparable results, but with lower differences between groups (control: 8.5±0.4 mm3; DME: 8.2±1.0 mm3; P=0.0267). CONCLUSION: DME eyes show significantly lower foveal thickness than matched controls after DME resolution achieved with one-year anti-VEGF therapy. Further investigation into the reasonsfor this presumable retinal atrophy using fluorescein angiography and functional parameters as well as establishing possible predictors is warranted. This finding should be considered during the treatment of DME.     

FOLFOX-6化疗方案联合贝伐单抗靶向治疗转移性结肠癌疗效及不良反应

目的：探索FOLFOX-6化疗方案与贝伐单抗靶向联合应用治疗转移性结肠癌的临床效果及不良反应。方法：将中国人民解放军第105医院2011年1月-2013年1月期间临床确诊并采取治疗的76例转移性结肠癌患者选为研究对象,并依据患者就诊顺序分成两组,对照组38例患者单用FOLFOX-6化疗方案,而观察组38例患者采用FOLFOX-6化疗方案与贝伐单抗靶向联合治疗,对比两组临床疗效及不良反应情况。结果： 观察组患者DCR（76.32%）和RR（60.51%）均较对照组（44.74%、23.68%）明显增加（P<0.05）。观察组患者PFS（9.87±1.23）月和OS（24.34±2.04）月均较对照组（6.45±1.10）月、（15.12±1.62）月明显延长（P<0.05）。两组患者主要不良反应胃肠道反应、神经毒性、手足综合症、骨髓抑制发生率比较,差异无统计学意义（P﹥0.05）。结论：FOLFOX-6化疗方案与贝伐单抗靶向联合应用治疗转移性结肠癌近期和远期疗效均优于单用化疗方案治疗,且安全性较高,值得临床借鉴和推广应用。     

雷公藤多苷治疗贝伐珠单抗导致蛋白尿1例

晚期大肠癌是我国常见的恶性肿瘤之一,其发病率和死亡率均位于恶性肿瘤的前列［1］。贝伐珠单抗是重组的人源化单克隆抗体,批准用于晚期大肠癌的治疗。该药临床常见的毒副反应有高血压、蛋白尿、出血、胃肠穿孔、血栓等。本例患者长期应用贝伐珠单抗,现就其毒副反应蛋白尿的治疗报告如下。     

The efficacy and safety of paclitaxel plus bevacizumab therapy in breast cancer patients with visceral crisis

BackgroundVisceral crisis in metastatic breast cancer (MBC) is defined as severe organ dysfunction requiring rapidly efficacious therapy. Although weekly paclitaxel plus bevacizumab (wPTX + BV) achieves a high response rate in human epidermal growth factor receptor 2 (HER2)-negative MBC, the efficacy and safety of wPTX + BV for visceral crisis is unclear.MethodsWe retrospectively investigated patients with MBC with visceral crisis who received wPTX + BV. Visceral crisis was defined as follows: liver dysfunction (aspartate or alanine aminotransferase >200 U/L or total bilirubin >1.5 mg/dl), respiratory dysfunction (carcinomatous lymphangiomatosis, SpO₂ <93% in ambient air or required thoracentesis), superior vena cava (SVC) syndrome, or bone marrow carcinomatosis. The primary outcome was the proportion of patients on-treatment with wPTX + BV after 12 weeks. We also investigated time to treatment failure (TTF), overall survival (OS), objective response rate (ORR), and adverse events.ResultsA total of 44 patients with respiratory dysfunction (n = 29), liver dysfunction (n = 10), bone marrow carcinomatosis (n = 7), and SVC syndrome (n = 2) were eligible for this investigation. The proportion of patients on-treatment with wPTX + BV after 12 weeks was 63% (30/44), and the other patients discontinued wPTX + BV because of adverse events (n = 5) and disease progression (n = 9). Median TTF and OS, and the ORR were 131 days and 323 days, and 41%, respectively. No treatment-related death occurred.Conclusion: wPTX + BV achieved favorable efficacy and safety for treating patients with visceral crisis and may therefore be considered an option for the treatment of this acutely severe clinical condition.     

Potent antitumor effects of bevacizumab in a microenvironment-dependent human lymphoma mouse model

We established a mouse model of microenvironment-dependent human lymphoma, and assessed the therapeutic potential of bevacizumab, an antitumor agent acting on the microenvironment. NOD/Shi-scid, IL-2Rγ(null) (NOG) mice were used as recipients of primary tumor cells from a patient with diffuse large B-cell lymphoma (DLBCL), which engraft and proliferate in a microenvironment-dependent manner. The lymphoma cells could be serially transplanted in NOG mice, but could not be maintained in in vitro cultures. Injection of bevacizumab together with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) significantly increased necrosis and decreased vascularization in the tumor, compared with CHOP alone. Levels of human soluble interleukin-2 receptor (sIL2R) in the serum of bevacizumab+CHOP-treated mice (reflecting the DLBCL tumor burden) were significantly lower than in CHOP recipients. Mice receiving bevacizumab monotherapy also showed significant benefit in terms of tumor necrosis and vascularization, as well as decreased serum sIL2R concentrations. The present DLBCL model reflects the human DLBCL in vivo environment more appropriately than current mouse models using established tumor cell lines. This is the first report to evaluate the efficacy of bevacizumab in such a tumor microenvironment-dependent model. Bevacizumab may be a potential treatment strategy for DLBCL patients.     

Identification of predictive circulating biomarkers of bevacizumab-containing regimen efficacy in pre-treated metastatic colorectal cancer patients

Background:

To identify whether circulating levels of angiogenesis-related factors may be predictive of bevacizumab efficacy in pre-treated metastatic colorectal cancer (mCRC) patients.

Methods:

Pre-treatment serum levels of 24 cytokines were measured using a multiplex bead assay (MBA) in 32 pre-treated mCRC patients treated with irinotecan plus bevacizumab-based salvage therapy. Macrophage-derived chemokine (MDC), interleukins (ILs) 8 and 6 levels were also validated by enzyme-linked immunosorbent assay (ELISA) at different time points during therapy.

Results:

Higher epidermal growth factor (EGF) and MDC baseline levels (2.2- and 1.4-fold, respectively) and lower IL-10, IL-6 and IL-8 levels (0.2-, 0.6-, and 0.6-fold, respectively, P<0.05) were observed in patients responding to therapy. Baseline levels of these five serum factors compose a risk signature that may define the subset of patients most likely to benefit from bevacizumab-based therapy in terms of response rate and survival times. A positive correlation was found between MBA and ELISA results (P<0.01). Treatment exposure increased MDC and had opposite effects on IL-8 levels, which were decreased (P<0.05).

Conclusion:

This study suggests that a set of inflammatory and angiogenesis-related serum markers may be associated with the efficacy of bevacizumab-containing regimen.