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。     

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...     

抗EGFR单抗类靶向药物在头颈部鳞癌综合治疗中的应用

头颈部肿瘤是世界上第6大常见的肿瘤。超过70%的头颈部肿瘤患者在首次确诊时即为局部晚期。尽管不断地努力改进治疗方法,但晚期病例的死亡率仍然居高不下。为了提高疗效,患者通常接受化疗、手术、放射治疗和分子靶向药物综合治疗。大量研究证实,表皮生长因子受体（epidermal growth factor receptor,EGFR）与肿瘤细胞的增殖和转移密切相关,EGFR在大多数头颈部肿瘤中高表达,对这些患者的预后有显著影响。抗EGFR单克隆抗体已经在一些国家被批准用于治疗局部晚期头颈鳞状细胞癌（head and neck squamous cell carcinoma,HNSCC）。本文综述了西妥昔单抗和尼妥珠单抗治疗HNSCC的研究进展。HNSCC的单克隆抗体靶向治疗,是选择西妥昔单抗还是尼妥珠单抗？本综述将围绕这一临床医生尤为关心的问题展开讨论。     

Perioperative Systemic Chemotherapy,Cytoreductive Surgery,and Hyperthermic Intraperitoneal Chemotherapy in Patients With Colorectal Peritoneal Metastasis: Results of the Prospective Multicenter Phase 2 COMBATAC Trial

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as parts of an interdisciplinary treatment concept including systemic chemotherapy can improve survival of selected patients with peritoneal metastatic colorectal cancer (pmCRC). Nevertheless, the sequence of the therapeutic options is still a matter of debate. Thus, the COMBATAC (COMBined Anticancer Treatment of Advanced Colorectal cancer) trial was conducted to evaluate a combined treatment regimen consisting of preoperative systemic polychemotherapy + cetuximab followed by CRS + HIPEC and postoperative systemic polychemotherapy + cetuximab.

Evaluation of survival across several treatment lines in metastatic colorectal cancer: Analysis of the FIRE-3 trial (AIO KRK0306)

BackgroundWe explored the impacts of sequential application of various treatment lines on survival kinetics. Therefore, differences in overall survival (OS) observed in FIRE-3 were investigated in the context of time and exposure to applied treatment.Patients and methodsOS analyses (stratified by treatment with FOLFIRI plus either cetuximab or bevacizumab) were performed according to time intervals as well as using a Cox model to define changes of hazard ratio (HR) over time.ResultsThe fraction of patients with systemic treatment and time on treatment markedly decreases over treatment lines and time. OS evaluation by a Cox model indicated a trend towards a non-proportional hazard between treatment arms (P = 0.12/P = 0.09 for KRAS–intention-to-treat (ITT)/all-RAS wild-type populations, respectively). To improve the fit of the model, a change-point (point of curve separation) was estimated at 22.6 months (day 687) after randomisation. The HR between the two arms before 22.6 months was not significantly different from one. However, markedly different survival kinetics in favour of the cetuximab arm were apparent after the change-point (KRAS-ITT: P = 0.0018; HR, 0.60 [95% confidence interval [CI], 0.44–0.83] and RAS: P = 0.0006; HR, 0.51 [95% CI, 0.35–0.75]).ConclusionThe differences in OS favouring the cetuximab arm become apparent about 22.6 months after randomisation, indicating that only those patients who survive 22.6 months after randomisation benefit from the superiority of the cetuximab arm. When OS curves separate, only few patients receive active systemic treatment in short courses, suggesting that earlier treatment effects are responsible for later kinetics of survival curves.     

Cetuximab with radiotherapy as an alternative treatment for advanced squamous cell carcinoma of the temporal bone

The prognosis of advanced temporal bone cancer is poor, because complete surgical resection is difficult to achieve. Chemoradiotherapy is one of the available curative treatment options; however, its systemic effects on the patient restrict the use of this treatment. A 69-year-old female (who needed peritoneal dialysis) presented at our clinic with T4 left external auditory canal cancer and was treated with cetuximab plus radiotherapy (RT). The primary lesion showed complete response. The patient is currently alive with no evidence of disease two years after completion of the treatment and does not show any late toxicity. This is the first advanced temporal bone cancer patient treated with RT plus cetuximab. Cetuximab plus RT might be a treatment alternative for patients with advanced temporal bone cancer.     

Effective Treatment of Lung Adenocarcinoma Harboring EGFR-Activating Mutation,T790M,and cis-C797S Triple Mutations by Brigatinib and Cetuximab Combination Therapy

IntroductionAcquired resistance to osimertinib mediated by EGFR cis-C797S is now a growing challenge. No effective treatment strategy is currently available to overcome cis-C797S–mediated resistance.MethodsIn this retrospective cohort study, 15 patients with advanced lung adenocarcinoma and EGFR-activating mutation, T790M, and cis-C797S after osimertinib progression were identified by targeted next-generation sequencing. Five of these patients received a combined therapy of brigatinib and cetuximab, and 10 patients received cisplatin-based doublet chemotherapy.ResultsAmong the five patients who were positive for EGFR 19del-T790M-cis-C797S mutations, and who received brigatinib and cetuximab combination therapy, three patients achieved partial response, and two had stable disease, resulting in an overall objective response rate of 60% and disease control rate of 100%. Among the 10 patients who were positive for EGFR 19del or L858R-T790M-cis-C797S mutations and received chemotherapy, only one patient achieved partial response, five had stable disease, and the other four did not benefit from chemotherapy, resulting in an overall objective response rate and disease control rate of 10% and 60%, respectively. The median progression-free survival of patients who received combined targeted therapy was 14 months, and 3 months for those treated with chemotherapy. No grade III to IV adverse events were observed in any patient.ConclusionsOur retrospective study provides clinical evidence that a combined targeted therapy of brigatinib and cetuximab could be of benefit and may potentially be an effective treatment strategy to improve survival outcomes in patients who acquire EGFR T790M-cis-C797S–mediated resistance to osimertinib.     

胃癌靶向药物治疗进展

胃癌是消化系统常见的恶性肿瘤之一,由于早诊率低,大多数患者在诊断时已经处于疾病中晚期。化疗是进展期胃癌的重要治疗方法,但是,细胞毒性药物联合方案并没有从根本上提高化疗有效率。分子靶向治疗是近年来在治疗血液系统肿瘤和实体瘤中涌现出的新治疗手段。随着对胃癌发生、发展和转移过程中分子生物学机制的研究,这种治疗手段也逐步应用于胃癌治疗的临床实践。这些靶向治疗策略主要包括:HER2单克隆抗体,表皮生长因子受体抑制剂,血管生成抑制剂,多靶点酪氨酸激酶抑制剂,细胞周期蛋白依赖性激酶(CDKs),mTOR抑制剂,c-Met抑制剂,基质金属蛋白酶抑制剂,IGF-1R抑制剂,HSP90抑制剂等。本文就进展期胃癌近年来分子靶向治疗的研究结果及相关进展作一综述。