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41.
Bianca van Veggel Adrianus J. de Langen Sayed M.S. Hashemi Kim Monkhorst Daniëlle A.M. Heideman Erik Thunnissen Egbert F. Smit 《Journal of thoracic oncology》2018,13(8):1222-1226
Introduction
EGFR exon 20 insertions comprise 4% to 9% of EGFR mutated NSCLC. Despite being an oncogenic driver, they are associated with primary resistance to EGFR tyrosine kinase inhibitors (TKIs). We hypothesized that dual EGFR blockade with afatinib, an irreversible EGFR TKI, and cetuximab, a monoclonal antibody against EGFR, could induce tumor responses.Methods
Four patients with EGFR exon 20 insertion–positive NSCLC were treated with afatinib 40 mg once daily and cetuximab 250 mg/m2 to 500 mg/m2 every 2 weeks.Results
All patients had stage IV adenocarcinoma of the lung harboring an EGFR exon 20 insertion mutation. Previous lines of treatment consisted of platinum doublet chemotherapy (n = 4) and EGFR TKI (n = 2). Three of four patients showed a partial response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Median progression-free survival was 5.4 months (95% confidence interval: 0.0 – 14.2 months; range 2.7 months – 17.6 months). Toxicity was manageable with appropriate skin management and dose reduction being required in two patients.Conclusions
Dual EGFR blockade with afatinib and cetuximab may induce tumor responses in patients with EGFR exon 20 insertion–positive NSCLC. 相似文献42.
Loredana Vesci Ferdinando Maria Milazzo Anna Maria Anastasi Fiorella Petronzelli Caterina Chiapparino Valeria Carollo Giuseppe Roscilli Emanuele Marra Laura Luberto Luigi Aurisicchio Maria Lucrezia Pacello Luigi Giusto Spagnoli Rita De Santis 《Oncotarget》2016,7(1):914-928
For locally advanced and metastatic head and neck squamous cell carcinoma (HNSCC), the current clinical use of Cetuximab in chemo/radiotherapy protocols is often associated to severe systemic toxicity. Here we report in vitro data in human FaDu pharynx SCC cells, showing that inactive concentrations of biotinylated Cetuximab (bCet) become active upon anchorage to AvidinOX on the surface of tumor cells. AvidinOX-anchored bCet induces apoptosis and DNA damage as well as specific inhibition of signaling, degradation and abrogation of nuclear translocation of EGFR. In the mouse model of FaDu cancer, we show that intra-tumor injection of AvidinOX allows anti-tumor activity of an otherwise inactive, intraperitoneally delivered, low dose bCet. Consistently with in vitro data, in vivo tumor inhibition is associated to induction of apoptosis, DNA damage and reduced angiogenesis. AvidinOX is under clinical investigation for delivering radioactive biotin to inoperable tumors (ClinicalTrials.gov ) and present data support its use for the local treatment of HNSCC in combination with systemic administration of low dose bCet. NCT02053324相似文献
43.
Broad Detection of Alterations Predicted to Confer Lack of Benefit From EGFR Antibodies or Sensitivity to Targeted Therapy in Advanced Colorectal Cancer
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44.
Cetuximab delivery and antitumor effects are enhanced by mild hyperthermia in a xenograft mouse model of pancreatic cancer
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Ryoichi Miyamoto Tatsuya Oda Shinji Hashimoto Tomohiro Kurokawa Yuki Inagaki Osamu Shimomura Yusuke Ohara Keiichi Yamada Yoshimasa Akashi Tsuyoshi Enomoto Mikio Kishimoto Hideto Yanagihara Eiji Kita Nobuhiro Ohkohchi 《Cancer science》2016,107(4):514-520
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. 相似文献
45.
Vijay Agarwal MD PhD Anand Subash MS DNB Ravi C. Nayar MS DNB DLO DCCF Vishal Rao US MS FRCS 《Journal of surgical oncology》2019,119(6):685-686
Epidermal growth factor receptor (EGFR) is overexpressed in 90% to 100% of squamous cell carcinoma of the head and neck (SCCHN). The overexpression of EGFR and its ligand transforming growth factor is associated with poorer survival. EGFR inhibitors such as Cetuximab (Erbitux) have shown a significant antitumoral effect in SCCHN and has improved locoregional control and as well as survival. Even though there was some success with Cetuximab, work with other EGFR inhibition has not been very fruitful and not really shown any promise. Mechanism of action of Cetuximab could be immune-mediated rather than EGFR inhibition and EGFR may not necessarily be a therapeutic target in SCCHN. 相似文献
46.
47.
Ken Okamoto Hiromichi Maeda Takeo Shiga Mai Shiga Ken Dabanaka Kazuhiro Hanazaki Michiya Kobayashi 《World journal of gastroenterology : WJG》2015,21(12):3746-3749
Monoclonal antibodies against epidermal growth factor receptor(EGFR) are used in the treatment of advanced colorectal cancer. However, these agents can induce severe dermatological side effects that discourage their administration in patients with chronic dermatological disease. EGFR plays a key role in normal skin development and immunological function, and is expressed in various tissues and organs, although contrarily, it is overexpressed in psoriasis-related skin lesions. Thus, discussion is ongoing regarding the putative pathological role and therapeutic potential of this protein. We herein report on a patient with advanced colon cancer and concomitant long-standing psoriasis vulgaris who received antiEGFR antibody monotherapy as a third-line treatment for metastatic disease. One week after the initiation of treatment, the patient’s skin lesions dramatically subsided and the improvement was sustained during therapy. Based on this case, we propose that anti-EGFR antibody therapy is not necessarily contraindicated in patients with psoriasis vulgaris. Moreover, the findings reaffirmed that EGFR is an important molecule in the pathology of psoriasis. 相似文献
48.
AIM: To investigate the correlation between Kirsten rat sarcoma viral oncogene homolog(KRAS) status and the therapeutic effects of anti-epidermal growth factor receptor(EGFR) monoclonal antibodies(Mo Abs) in metastatic colorectal cancer(m CRC).METHODS: Randomized controlled trials(RCTs) were identified and the association between KRAS mutation and clinical outcome in m CRC patients treated with anti-EGFR Mo Abs was investigated. Ten RCTs wereincluded in this meta-analysis. Progression-free survival and overall survival were used to assess the strength of the relationship between KRAS mutation and clinical outcome.RESULTS: In first-line treatment, survival benefit was confined to patients with wild-type KRAS. Chemotherapy regimens and angiogenesis inhibitor treatment influenced the results of the analysis. Wildtype KRAS m CRC patients did not seem to benefit from oxaliplatin-based chemotherapy(PFS: HR = 0.88, 95%CI: 0.70-1.10; OS: HR = 0.93, 95%CI: 0.82-1.04). Clinical benefit in m CRC patients was limited to therapeutic regimens which included anti-EGFR Mo Abs and fluorouracil-based therapy(PFS: HR = 0.77, 95%CI: 0.69-0.86; OS: HR = 0.85, 95%CI: 0.75-0.95). When anti-EGFR Mo Abs were used as second- or further-line treatment, clinical benefit was still confined to patients with wild-type KRAS. CONCLUSION: KRAS status is a potential predictive marker of clinical benefit due to anti-EGFR Mo Ab therapy in m CRC patients. 相似文献
49.
目的建立结直肠癌裸鼠移植肿瘤模型,用小动物18F-FDG PET/CT技术评价西妥昔单抗对人结直肠癌移植肿瘤的影响。
方法BALB/c裸鼠皮下分别接种人结直肠癌细胞HCT116、LIM1215,建立HCT116与LIM1215两种荷瘤裸鼠模型。将成瘤后的模型分为对照组和西妥昔单抗治疗组(n=5),并且全程观察肿瘤体积变化情况。给药1周后采用小动物18F-FDG PET/CT技术评价实体肿瘤模型,并测量各组织与器官的18F-FDG最大每克组织摄取率。
结果小动物18F-FDG PET/CT成像显示裸鼠接种部位肿瘤内放射性摄取值增高,LIM1215与HCT116肿瘤模型的治疗组与对照组相比,肿瘤/组织或器官18F-FDG摄取比率均普遍降低,其中肿瘤/颈肌、肿瘤/心脏与肿瘤/肝脏比值差异有统计学意义(P=0.047、0.008、0.024),但两种肿瘤模型的肿瘤体积测量结果均显示,治疗组与对照组的肿瘤生长趋势差异无统计学意义。
结论在西妥昔单抗对结直肠癌裸鼠移植肿瘤模型的治疗实验中,西妥昔单抗对肿瘤生长尚未有明显抑制作用时,小动物18F-FDG PET/CT可监测到肿瘤葡萄糖代谢的变化。 相似文献
50.
Kristin Gurtner Yvonne Deuse Rebecca Bütof Katja Schaal Wolfgang Eicheler Reinhard OertelReidar Grenman Howard ThamesAla Yaromina Michael Baumann Mechthild Krause 《Radiotherapy and oncology》2011,99(3):323-330