西妥昔单抗联合同步放化疗治疗局部头颈部鳞癌的疗效及对患者睡眠质量的影响

目的:研究西妥昔单抗联合同步放化疗治疗局部头颈部鳞癌的疗效及对患者睡眠质量的影响.方法:选取珠海市第二中医院收治的局部头颈部鳞癌患者100例作为研究对象,按治疗方案分为观察组和对照组,每组50例.观察组行西妥昔单抗联合同步放化疗,对照组行单一同步放化疗,分析比较2组患者临床疗效.结果:观察组治疗总有效率比对照组高,治疗...     

Cetuximab delivery and antitumor effects are enhanced by mild hyperthermia in a xenograft mouse model of pancreatic cancer

Even with current promising antitumor antibodies, their antitumor effects on stroma‐rich solid cancers have been insufficient. We used mild hyperthermia with the intent of improving drug delivery by breaking the stromal barrier. Here, we provide preclinical evidence of cetuximab + mild hyperthermia therapy. We used four in vivo pancreatic cancer xenograft mouse models with different stroma amounts (scarce, MIAPaCa‐2; moderate, BxPC‐3; and abundant, Capan‐1 and Ope‐xeno). Cetuximab (1 mg/kg) was given systemically, and the mouse leg tumors were concurrently heated using a water bath method for 30 min at three different temperatures, 25°C (control), 37°C (intra‐abdominal organ level), or 41°C (mild hyperthermia) (n = 4, each group). The evaluated variables were the antitumor effects, represented by tumor volume, and in vivo cetuximab accumulation, indirectly quantified by the immunohistochemical fluorescence intensity value/cell using antibodies against human IgG Fc. At 25°C, the antitumor effects were sufficient, with a cetuximab accumulation value (florescence intensity/cell) of 1632, in the MIAPaCa‐2 model, moderate (1063) in the BxPC‐3 model, and negative in the Capan‐1 and Ope‐xeno models (760, 461). By applying 37°C or 41°C heat, antitumor effects were enhanced shown in decreased tumor volumes. These enhanced effects were accompanied by boosted cetuximab accumulation, which increased by 2.8‐fold (2980, 3015) in the BxPC‐3 model, 2.5‐ or 4.8‐fold (1881, 3615) in the Capan‐1 model, and 3.2‐ or 4.2‐fold (1469, 1922) in the Ope‐xeno model, respectively. Cetuximab was effective in treating even stroma‐rich and k‐ras mutant pancreatic cancer mouse models when the drug delivery was improved by combination with mild hyperthermia.     

西妥昔单抗联合化疗治疗转移性结直肠癌的临床观察

目的观察西妥昔单抗与奥沙利铂/5-FU/FA联合治疗转移性结直肠癌的近期疗效及毒性反应。方法对11例转移性结直肠癌(MCRC)患者采用西妥昔单抗与奥沙利铂/5-FU/FA化疗联合方案,应用2周期后评价近期疗效及毒性反应。西妥昔单抗首次推荐剂量为400 mg/m~2,以后每周剂量为250 mg/m~2,奥沙利铂/5-FU/FA化疗剂量采用FOLFOX4方案。结果11例患者均完成西妥昔单抗连续6周用药,奥沙利铂/5-FU/FA化疗2周期(每2周重复1次),无CR病例,2例PR(18.18%),4例SD(36.36%),5例PD(45.45%),疾病控制(PR SD)率54.55%。治疗过程中出现的毒性反应为3～4度的痤疮样皮疹,另外有恶心、呕吐、腹痛和虚弱,2～3度白细胞下降。全组患者无过敏反应。结论西妥昔单抗可提高肿瘤对放化疗的敏感性。采用西妥昔单抗与奥沙利铂联合治疗11例转移性结直肠癌患者,取得初步疗效和安全性观察,且不因联合化疗而增加毒性反应,耐受性良好。     

Locoregional therapy and systemic cetuximab to treat colorectal liver metastases

AIM: To investigate efficacy and safety of second-line treatment with irinotecan-loaded drug-eluting beads (DEBIRI) and cetuximab (DEBIRITUX) of unresectable colorectal liver metastases.METHODS: Patients with the following characteristics were included in the study: unresectable hepatic metastases from colorectal carcinoma (CRC-LM), progression after first line chemotherapy (any type of chemotherapeutic drug and combination was allowed), second line treatment (mandatory), which included for each patient (unregarding the KRas status) two cycles of DEBIRI (using 100-300 μm beads loaded with irinotecan at a total dose 200 mg) followed by 12 cycles of cetuximab that was administered weekly at a first dose of 400 mg/m² and then 250 mg/m²; good performance status (0-2) and liver functionality (alanine aminotransferase and gamma-glutamyl transferase not exceeding three times the upper limit of normal, total bilirubin not exceeding 2.5 mg/mL). Data were collected retrospectively and included: tumor response (evaluated monthly for 6 mo then every 3 mo), overall response rate (ORR), KRas status, type and intensity of adverse events (G according to the Common Terminology Criteria for Adverse Events v3.0, CTCAE), overall survival (OS) and progression free survival (PFS).RESULTS: Forty consecutive cases of CRC hepatic metastases were included in the study. Median duration of DEBIRITUX was 4.4 mo (range, 4.0-6.5). Sixteen patients (40%) received the planned 2 cycles of DEBIRI and an average of 10 cetuximab cycles. ORR of the whole sample was 50%, in particular 4 patients were complete responders (10%) and 16 (40%) partial responders. The most observed side effects (G2) were: post-embolization syndrome (30%), diarrhea (25%), skin rushes (38%) and asthenia (35%). The retrospective evaluation of KRas status (24 wild type, 16 mutated) showed that the group of patients with wild type KRas had ORR significantly higher than mutant KRas. Median follow-up was 29 mo (8-48 range); median PFS was 9.8 mo and OS was 20.4 mo. Future randomized trials are required in this setting to establish a role for DEBIRITUX compared with systemic chemotherapy.CONCLUSION: DEBIRITUX seems to be efficacious after first line chemotherapy for the treatment of unresectable CRC-LM.     

The anti-EGFR antibody cetuximab sensitizes human head and neck squamous cell carcinoma cells to radiation in part through inhibiting radiation-induced upregulation of HIF-1α

In this study, we investigated the mechanisms underlying cetuximab-mediated radiosensitization of HNSCC. Irradiation of HNSCC cells upregulated hypoxia-inducible factor-1 alpha (HIF-1α) via a mechanism involving de novo synthesis of HIF-1α protein. Radiation-induced upregulation of HIF-1α was completely abolished by concurrent treatment of HNSCC cells with cetuximab. Experimental elevation of constitutively expressed HIF-1α abolished cetuximab-mediated radiosensitization in HNSCC cells, whereas downregulation of HIF-1α by siRNA or a small molecule inhibitor enhanced responses of cetuximab-resistant HNSCC cells to cetuximab plus radiation. Our data suggest that cetuximab sensitizes cancer cells to ionizing radiation in part through inhibition of radiation-induced upregulation of HIF-1α.     

表皮生长因子受体抑制剂在非小细胞肺癌治疗中的研究进展

化疗一直是晚期非小细胞肺癌(NSCLC)的主要治疗手段之一,但是治疗的有效率仅为30％左右,且具有较大的不良反应,耐药和血液学的不良反应是患者预后不良的主要原因之一.随着分子生物标记如表皮生长因子受体(EGFR)等的发现和相应靶向药物的研发与批准应用,肺癌的治疗正在发生重大变化.大量研究证实EGFR抑制剂靶向治疗能改善NSCLC患者的疾病无进展期和生活质量,而正确的选择合适的患者是靶向治疗成功的关键.本文将对EGFR的组成及活化、检测方法、EGFR靶向药物在NSCLC治疗中的作用以及获得性耐药患者的治疗进展进行综述.     

放化疗联合西妥昔单抗治疗非小细胞肺癌的临床研究

目的 评价放化疗联合西妥昔单抗治疗不可切除进展期非小细胞肺癌(NSCLC)的安全性和有效性.方法 回顾性分析了2007年2月至2010年1月接受放化疗联合或不联合西妥昔单抗治疗的不可切除ⅢA或ⅢB期NSCLC.患者生存以Kaplan-Meier曲线进行描述,Log-rank检验进行差异性分析.结果 共有243例不可切除的ⅢA或ⅢB期NSCLC接受放化疗联合或不联合西妥昔单治疗,其中177例被纳入分析.西妥昔单抗组中位生存时间为23个月(95％ CI:21～25),对照组中位生存时间为21个月(95％ CI:19～23).两组患者中位生存时间差异有统计学意义(P=0.008).结论 在卡铂加培美曲塞联合放疗的基础上增用西妥昔单抗,可能能够改善患者的预后.此结果还需要大样本的随机对照临床研究的证实.