Treatment of malignant, non-resectable, epithelial origin esophageal tumours with the humanized anti-epidermal growth factor antibody nimotuzumab combined with radiation therapy and chemotherapy.

Ramos-Suzarte, Mayra; Lorenzo-Luaces, Patricia; Lazo, N González; Pérez, Mayté Lima; Soriano, Jorge Luis; González, Carmen Elena Viada; Hernadez, Ivis Mendoza; Albuerne, Yisel Ávila; Moreno, Beatriz Paredes; Álvarez, Eduardo Santiesteban; Callejo, Idael Pineda; Alert, J; Martell, Juan Antonio; González, Y.; Gonzalez, Yulainis Santiesteban; Vega, Horacio Astudillo de la; Ruiz‐García, Erika; Ramos, Tania Crombet

doi:10.4161/cbt.19849

Cited by 56 publications

(49 citation statements)

References 32 publications

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“…An open, uncontrolled phase II study indicated that the combination of nimotuzumab with concurrent chemoradiation was tolerated reasonably well in patients with advanced or metastatic ESCC, and increased the efficacy of treatment (34). Ramos-Suzarte et al (32) evaluated the adverse events of nimotuzumab combined with chemotherapy, radiotherapy or chemoradiotherapy in 835 patients pathologically diagnosed with malignant tumors in stage II-IV with metastasis or advanced carcinomas, and indicated that nimotuzumab with chemoradiotherapy was tolerated.…”

Section: Discussionmentioning

confidence: 99%

“…Nimotuzumab is well-tolerated, and efficacious against a number of tumor types (18,(30)(31)(32). Numerous studies have demonstrated that for patients with advanced carcinoma, nimotuzumab combined with chemotherapy, radiotherapy or chemoradiotherapy was effective, and that it was well-tolerated and safe for conditions such as glioblastoma multiforme (GBM) and esophageal squamous cell cancer (ESCC); in combination with radiation therapy, nimotuzumab demonstrated few side effects (19) and improved the disease control rate in patients with GBM compared with radiation therapy alone (33).…”

Section: Discussionmentioning

confidence: 99%

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Antitumor activity of nimotuzumab in combination with cisplatin in lung cancer cell line A549 inï¿½vitro

Yang

Zhou

et al. 2018

Oncol Lett

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Abstract. Nimotuzumab, a humanized IgG1 monoclonal antibody against epidermal growth factor receptor (EGFR), increases radiosensitivity in lung cancer. Cisplatin is an effective antitumor agent in lung cancer. In the present study, the antitumor activity of nimotuzumab combined with cisplatin was investigated in A549 lung cancer cells. Viability, cell cycle distribution and cyclin D1 expression were assessed following treatment with nimotuzumab alone, cisplatin alone, nimotuzumab in combination with cisplatin, and nimotuzumab followed sequentially by cisplatin. The inhibitory effect on cell viability of nimotuzumab sequentially followed by cisplatin was higher compared with cisplatin alone (82.17±1.62 vs. 56.97±1.42%). Compared with treatment by cisplatin alone, cell cycle analysis by flow cytometry demonstrated that the percentage of cells in the G 0 /G 1 phase was increased when A549 cells were treated with nimotuzumab followed sequentially by cisplatin (P<0.01). However, the proportion of cells in G 0 /G 1 phase was decreased when A549 cells were treated with nimotuzumab and cisplatin simultaneously compared with cisplatin alone (P<0.05). Cyclin D1 expression was decreased in all chemotherapy treatment groups; the most significant decrease was in A549 cells treated with nimotuzumab followed sequentially by cisplatin. Nimotuzumab may enhance the antitumor activity of cisplatin on A549 cells. The cell cycle arrest at G 0 /G 1 observed may have been due to decreased cyclin D1 levels. Potential antagonism was identified when A549 cells were treated with nimotuzumab and cisplatin simultaneously, indicating that targeted therapy may be more effective when administered prior to conventional chemotherapy. IntroductionLung cancer has been the most common cancer worldwide, and the leading cause of cancer-associated mortality, since 1985 (1). The 5-year survival rate for lung carcinoma overall is poor, at 16-17% (2). Surgery is not suitable for the majority of patients with lung cancer, as diagnoses are often obtained at advanced disease stages. The standard of care for advanced non-small cell lung cancer (NSCLC) is cisplatin in combination with 1 to 3 of the following drugs: Paclitaxel, gemcitabine and docetaxel (3). The efficacy of chemotherapy is limited due to its side effects and the lack of response in certain sub-populations of patients. Research efforts have focused on identifying molecular targets and developing molecular-targeted therapies based on the understanding of the molecular abnormalities associated with lung cancer (4-6).Insight into the pathobiology of NSCLC has facilitated the development of targeted molecular therapies that target specific mutations that serve critical roles in the progression to aggressive disease. Mutations in the epidermal growth factor receptor (EGFR), KRAS and anaplastic lymphoma kinase (ALK) genes are mutually exclusive in patients with NSCLC, and targeted therapy may be affected due to the existence of one mutation in lieu of another. Therefore, the detection of these mutati...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Antitumor activity of nimotuzumab in combination with cisplatin in lung cancer cell line A549 inï¿½vitro

Yang

Zhou

et al. 2018

Oncol Lett

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“…Its use is supported by a wide clinical experience, showing efficacy to treat patients with head and neck cancer, 7 high grade glioma 8 and esophageal tumors. 9 Additional clinical trials are being performed. 10,11 One distinctive feature of nimotuzumab among anti-EGFR therapeutic agents is its low toxicity.…”

Section: Introductionmentioning

confidence: 99%

Delineating the functional map of the interaction between nimotuzumab and the epidermal growth factor receptor

Tundidor

García-Hernández

Pupo

et al. 2014

mAbs

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“…In several phase II studies, nimotuzumab concurrently with chemotherapy and radiotherapy have been proven to be safe and effective in the treatment of esophageal cancer [10][11][12][13]. Ramos-Suzarte and colleagues [10] compared nimotuzumab plus concurrent chemoradiotherapy with 5-fluorouracil and cisplatin in the treatment of stage III/IV esophageal squamous cell carcinoma patients and resulted in a great improvement in efficacy (48 vs 15%, P = 0.014), the disease control rate (61 vs 27%, P = 0.017) and median overall survival (8.1 vs 3.0 months) in the nimotuzumab group. However, the safety and efficacy of the combination of nimotuzumab with neoadjuvant chemoradiotherapy (NimonCRT) in patients with resectable esophageal squamous cell carcinoma is unclear.…”

Section: Introductionmentioning

confidence: 99%

Neoadjuvant nimotuzumab plus chemoradiotherapy compared to neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma

Chen

Hao

et al. 2018

Oncotarget

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Neoadjuvant therapy improves long-term locoregional control and overall survival after surgical resection for esophageal cancer, and neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) are commonly used in clinical practice. Nimotuzumab is a humanized monoclonal antibody against epidermal growth factor receptor (EGFR), the efficacy of nimotuzumab added to nCRT for esophageal cancer is uncertain. We conducted this retrospective study in which combining neoadjuvant treatment of nimotuzumab with chemoradiotherapy (NimonCRT) is compared with nCRT and nCT for patients with potentially resectable locally advanced esophageal squamous cell carcinoma. One hundred ninety-five patients received neoadjuvant therapy and 172 (88.2%) underwent esophagectomy. Surgical resection was performed in 94.4% after Nimo-nCRT, versus 92.5% after nCRT and 83.5% after nCT (P = 0.026). The R0 resection rate was 100% after Nimo-nCRT, 95.9% after nCRT and 92.6% after nCT (P = 0.030). Pathological complete response (pCR) was achieved in 41.2% after Nimo-nCRT, versus 32.4% after nCRT and 14.8% after nCT (P = 0.0001). Lymph-node metastases were observed in 29.4% in the Nimo-nCRT group, versus 21.6% in the nCRT group and 35.8% in the nCT group (P = 0.093). More patients in the Nimo-nCRT and nCRT group developed grade 3 esophagitis compared to those in the nCT group, P = 0.008. There was no difference in surgical complications between the treatment groups. nCRT results in improved R0 resection, higher pCR rate, and a lower frequency of lymph node metastases compared to nCT, adding nimotuzumab to nCRT is safe and appears to facilitate complete resection and increase the pCR rate.

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Treatment of malignant, non-resectable, epithelial origin esophageal tumours with the humanized anti-epidermal growth factor antibody nimotuzumab combined with radiation therapy and chemotherapy.

Abstract: Nimotuzumab plus chemoradiotherapy was safe and provided statistically significant objective response. A Phase III in patients with similar characteristics will be launched.

Cited by 56 publications

References 32 publications

Antitumor activity of nimotuzumab in combination with cisplatin in lung cancer cell line A549 inï¿½vitro

Antitumor activity of nimotuzumab in combination with cisplatin in lung cancer cell line A549 inï¿½vitro

Delineating the functional map of the interaction between nimotuzumab and the epidermal growth factor receptor

Neoadjuvant nimotuzumab plus chemoradiotherapy compared to neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma

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