anti-angiogeneic therapy

  • 文章类型: Editorial
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  • 文章类型: Case Reports
    在过去的五年里,免疫检查点抑制剂阿妥珠单抗和抗血管生成药物贝伐单抗的联合出现改变了不可切除肝细胞癌的治疗方法.随着患者预后的改善,医疗保健专业人员在血液透析中会更频繁地遇到合并肝细胞癌和终末期肾病的患者.我们在文献中介绍了第一例58岁的男性多灶性肝细胞癌患者进行常规血液透析,该患者成功使用阿特珠单抗和贝伐单抗治疗,部分缓解,病情稳定两年。患有一年级疲劳的人,2级高血压和最终3级伤口感染导致贝伐单抗停止。阿替珠单抗单药治疗疾病进展后,所有化疗都停止了.我们在对阿特珠单抗和贝伐单抗在血液透析患者中使用的最新文献的综述中嵌入了这种情况,并得出结论,这两种靶向疗法都可以安全地用于这些患者。我们建议肿瘤科和肾脏科团队联合密切管理这些患者,在开始阿妥珠单抗和贝伐单抗治疗之前进行初始心血管危险分层。在治疗期间,应该定期监测血压,如果患者在透析团队的指导下出现少尿症,如果需要保留残余肾功能,则为蛋白尿。
    In the last five years, the advent of combination immune checkpoint inhibitor atezolizumab and anti-angiogenic agent bevacizumab has transformed treatment of unresectable hepatocellular carcinoma. As patient outcomes improve, healthcare professionals will more frequently encounter patients with concomitant hepatocellular cancer and end stage kidney disease on haemodialysis. We present the first case in the literature of a 58-year-old male with multifocal hepatocellular carcinoma undertaking regular haemodialysis who was successfully treated with atezolizumab and bevacizumab with a partial response and stable disease for two years, who suffered grade 1 fatigue, grade 2 hypertension and eventually grade 3 wound infection leading to cessation of bevacizumab. After disease progression on atezolizumab monotherapy, all chemotherapy was stopped. We embed this case in a review of the current literature of atezolizumab and bevacizumab use in patients undertaking haemodialysis and conclude that both targeted therapies may be safely used in these patients. We recommend joint close management of these patients between oncology and nephrology teams, with initial cardiovascular risk stratification before commencing atezolizumab and bevacizumab therapy. During therapy, there should be regular monitoring of blood pressure, or proteinuria if the patient is oliguric under guidance of the dialysis team if preservation of residual renal function is required.
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  • 文章类型: Journal Article
    近年来,免疫治疗改变了非小细胞肺癌(NSCLC)的治疗策略,其中使用最多的是抗PD-1/PD-L1抗体。然而,大多数NSCLC患者未从免疫检查点抑制剂(ICIs)获益.血管异常是大多数实体瘤的标志,并促进免疫逃避。因此,联合抗血管生成治疗可能会提高抗PD-1/PD-L1抗体的有效性.在本文中,说明了抗血管生成剂与抗PD-1/PD-L1抗体联合的机制,此外,相关临床研究和预测免疫治疗生物标志物进行总结和分析,为NSCLC患者提供更多的治疗选择。
    Immunotherapy has changed the treatment strategy of non-small cell lung cancer (NSCLC) in recent years, among which anti-PD-1/PD-L1 antibodies are the most used. However, the majority of patients with NSCLC do not derive benefit from immune checkpoint inhibitors (ICIs). Vascular abnormalities are a hallmark of most solid tumors and facilitate immune evasion. Thus, combining antiangiogenic therapies might increase the effectiveness of anti-PD-1/PD-L1 antibodies. In this paper, the mechanisms of anti-angiogenic agents combined with anti-PD-1/PD-L1 antibodies are illustrated, moreover, relevant clinical studies and predictive immunotherapeutic biomarkers are summarized and analyzed, in order to provide more treatment options for NSCLC patients.
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  • 文章类型: Journal Article
    患有复发性和转移性实体瘤的儿童和青少年预后较差。先前的1期研究(ANGIO1)用贝伐单抗靶向血管生成,索拉非尼,和环磷酰胺,在一部分患者中表现出活动信号。在这里,我们报告了以推荐的2期剂量治疗的一组儿科和年轻成年患者的结果。
    回顾了接受ANGIO1治疗的难治性或复发性实体瘤患者的电子病历。治疗周期持续21天,包括贝伐单抗,索拉非尼,和环磷酰胺.使用不良事件通用术语标准评估毒性,v5.0.使用实体瘤中的反应评价标准(RECIST1.1)评价反应。
    39名患者(22名男性,17名女性;中位年龄15岁;范围1-22岁)接受治疗方案。最常见的诊断包括骨肉瘤(n=21;14尤因肉瘤,7个骨肉瘤)和软组织肉瘤(n=9;2个横纹肌肉瘤,3滑膜肉瘤,2个促纤维增生性小圆细胞肿瘤,和2个高级别肉瘤)。最常见的3级非血液学毒性包括高血压(2,5.4%)和血尿(2,5.4%)。5例患者(13.5%)有气胸(3例在进行性疾病,1肺活检后,和1自发)。常见的3/4级血液学毒性为淋巴细胞减少症(19,51%)和白细胞减少症(13,35%)。16例患者(43.2%)出现了2级或以下的掌-足红感觉障碍。总共施用297个周期。23名患者需要减少环磷酰胺的剂量,治疗期间索拉非尼或贝伐单抗,所有患者在调整剂量后仍能获得临床获益.1例患者(尤因肉瘤)在11个周期后达到完全缓解;2例患者(尤因肉瘤,高级别肉瘤)分别在第2和第4周期后获得部分缓解,并且有20例患者的疾病稳定为最佳缓解。
    静脉注射贝伐单抗联合口服索拉非尼和节拍环磷酰胺是耐受的,需要最少的支持治疗或额外的临床就诊。在超过一半的治疗患者中观察到疾病长时间稳定。骨肉瘤患者表现出活动信号,表明在前期设置中纳入治疗作为维持方案可能有益,或作为姑息治疗方案。
    UNASSIGNED: Children and adolescents with recurrent and metastatic solid tumors have a poor outcome. A previous phase 1 study (ANGIO1) targeting angiogenesis with bevacizumab, sorafenib, and cyclophosphamide, demonstrated a signal of activity in a subset of patients. Here we report the results of a cohort of pediatric and young adult patients treated at the recommended phase 2 doses.
    UNASSIGNED: Electronic medical records of patients with refractory or recurrent solid tumors who received ANGIO1 therapy were reviewed. Treatment cycles lasted 21 days and included bevacizumab, sorafenib, and cyclophosphamide. Toxicities were assessed using Common Terminology Criteria for Adverse Events, v5.0. Responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST1.1).
    UNASSIGNED: Thirty-nine patients (22 male, 17 female; median age 15 years; range 1-22 years) received the treatment regimen. The most common diagnoses included bone sarcomas (n=21; 14 Ewing sarcoma, 7 osteosarcoma) and soft tissue sarcomas (n=9; 2 rhabdomyosarcoma, 3 synovial sarcoma, 2 desmoplastic small round cell tumors, and 2 high-grade sarcoma). The most common Grade 3 non-hematologic toxicities included hypertension (2, 5.4%) and hematuria (2, 5.4%). Five patients (13.5%) had a pneumothorax (3 at progressive disease, 1 post lung biopsy, and 1 spontaneous). Common Grade 3/4 hematologic toxicities were lymphopenia (19, 51%) and leukopenia (13, 35%). Sixteen patients (43.2%) developed palmar-plantar erythrodysesthesia Grade 2 or less. A total of 297 cycles were administered. Twenty-three patients required a dose reduction of cyclophosphamide, sorafenib or bevacizumab during therapy, all of whom continued to have clinical benefit following dose modification. One patient (Ewing sarcoma) achieved a complete response after 11 cycles; 2 patients (Ewing sarcoma, high grade sarcoma) achieved a partial response following cycles 2 and 4, respectively and 20 patients had stable disease as a best response.
    UNASSIGNED: Intravenous bevacizumab combined with oral sorafenib and metronomic cyclophosphamide was tolerated and required minimal supportive care or additional clinic visits. Disease stabilization for prolonged time periods was observed in greater than half of the treated patients. Patients with bone sarcoma demonstrated a signal of activity suggesting possible benefit from incorporation of the therapy as a maintenance regimen in upfront setting, or as a palliative regimen.
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