Treatment of non-small cell lung cancer with intensity-modulated radiation therapy in combination with cetuximab: the NEAR protocol (NCT00115518)

Jensen, Alexandra D; Münter, Marc W.; Bischoff, Helge; Haselmann, Renate; Timke, Carmen; Krempien, Robert; Sterzing, Florian; Nill, S.; Heeger, Steffen; Hoess, Angelika; Haberkorn, Uwe; Huber, Peter E.; Steins, Martin; Thomas, Michael; Debus, Jürgen; Herfarth, Klaus

doi:10.1186/1471-2407-6-122

Cited by 30 publications

(12 citation statements)

References 16 publications

(15 reference statements)

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“…Combination of cetuximab and radiation resulted toxicity mainly in oesophagitis and pneumonitis as toxicity. Proportion of these adverse events was similar to those obtained with radiotherapy alone in previous clinical studies [96][97][98][99][100][101][102]. Only one trial compared directly cetuximab and chemoradiotherapy to chemoradiotherapy.…”

Section: Cetuximab and Radiotherapysupporting

confidence: 75%

Monoclonal Antibodies: An Emerging Class of Therapeutics in Non Small Cell Lung Cancer

Guilleminault¹,

Lemarié²,

Heuzé-Vourc’h³

2012

JCT

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Lung cancer is the leading cause of cancer-related deaths in industrialized countries and non small cell lung cancer (NSCLC) accounts for 85% of all lung cancers. Cisplatin doublet based chemotherapy, which is the recommended regimen in first line therapy in advanced or metastatic NSCLC, improves survival but in low proportion. Monoclonal antibodies (mAbs) are a novel promising therapeutic class used with great results in inflammatory diseases such as rheumatoid arthritis. Antibodies are natural proteins with modular structure, specific pharmacodynamics and pharmacokinetics and possibly produced against any antigens, thus giving them several advantages over small drug therapeutics. In solid tumors, therapeutic mAbs improved progression free survival (PFS) and overall survival (OS) of patients with breast and colon cancers and had considerably changed the treatment in clinical practice. In NSCLC, bevacizumab, an anti-VEGF mAb, and cetuximab, an anti-EGFR mAb, are the most studied antibodies. Bevacizumab acts on angiognenesis and improved PFS of non squamous NSCLC but in low proportion as shown in two large phase III trials. It was approved by European Medicines Agency (EMEA) and Food and Drug administration (FDA) as a first line therapy in combination with cisplatin doublet chemotherapy. Cetuximab slightly enhanced OS but did not improve PFS in two large phase III trials. These results added to high adverse effect lead to cetuximab refusal by EMEA and FDA in NSCLC. At first glance, the results of mAbs in NSCLC are somewhat disappointing, in contrast to the benefits obtained with mAb treatments in other solid tumors. However, many other mAbs directed against novel targets, such as IGF1-R or CTLA-4, and new mAbs targeting VEGFR and EGFR pathways with different pharmacodymamical and pharmacokinetic properties are under evaluation and may change our vision of taking care of patients with NSCLC. In conclusion, it seems that mAbs therapy in NSCLC clearly marks the start of a new era in NSCLC treatment, with promises in improving patient survival and quality of life.

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Section: Cetuximab and Radiotherapysupporting

confidence: 75%

Monoclonal Antibodies: An Emerging Class of Therapeutics in Non Small Cell Lung Cancer

Guilleminault¹,

Lemarié²,

Heuzé-Vourc’h³

2012

JCT

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“…In the CALGB 30407 study, a phase II trial, cetuximab did not seem to have an additive effect if it was given concurrent with the irradiation and pemetrexed and carboplatin [54]. Several trials are ongoing and are summarized in Table 2 [51][52][53][54][55][56][57]. It is to be expected that the effect on systemic tumor control will be limited but for a subgroup of patients it might be beneficial [57].…”

Section: Cetuximabmentioning

confidence: 99%

Chemoradiation therapy in nonsmall cell lung cancer

Baas¹,

Belderbos

Heuvel³

2011

Current Opinion in Oncology

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Our evaluation indicates that there are quite a number of positive developments in the treatment of locally advanced NSCLC but there is still much to improve. Variables such as patient condition, tumor biology, dose of radiation therapy, method of application (intensity modulated radiation therapy, four-dimensional planning) and dose of chemotherapy all influence treatment outcome and should be taken into account in designing the best treatment. Well-defined studies should be undertaken balancing the possible positive effect of therapy and toxicity.

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“…En el carcinoma de pulmón no microcítico (CPNM), varios estudios en marcha están evaluando la seguridad y eficacia de cetuximab y erlotinib asociados a RT (o a radioquimioterapia) [17][18][19][20] . El grupo norteamericano RTOG evalúa en un estudio fase II los efectos de cetuximab en asociación con RT y QT en pacientes con CPNM localmente avanzado.…”

Section: Bonner Y Col Publicaron En 2006unclassified

Interaction of radiotherapy and new agents with molecular targets

López

Eito

Solá

et al. 2009

An Sist Sanit Navar

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RESUMENLa radioquimioterapia supuso uno de los mayores logros en el tratamiento del cáncer en las últimas déca-das, aunque con una importante toxicidad para los enfermos. La investigación desarrollada recientemente en la biología molecular del cáncer ha permitido conocer los cambios genéticos y moleculares que determinan la transformación maligna celular, lo que ha conducido a identificar moléculas claves convirtiéndolas en dianas moleculares además de revolucionar los conceptos radiobiológicos de respuesta celular a las radiaciones y de radiorresistencia.Los nuevos agentes contra dianas moleculares poseen mayor especificidad y menos efectos adversos, lo que les hace más atractivos que la quimioterapia para ser combinados con radioterapia. Pueden actuar inhibiendo las señales de transducción intracelular, modulando el ciclo celular, la apoptosis o inhibiendo la angiogénesis. El efecto de la radioterapia puede potenciarse a través de una inhibición de la repoblación celular, mejoría de la oxigenación tumoral, redistribución durante el ciclo celular, inhibición de la invasión y metástasis, y aumento de la radiosensibilidad. Los datos disponibles apoyan su eficacia y aplicabilidad en estudios preclíni-cos y clínicos en diversos modelos tumorales y abren una vía esperanzadora de cambio en el tratamiento del cáncer.Palabras clave. Nuevas dianas moleculares. Interacciones con la radioterapia. Radiorresistencia. Radiosensibilidad. ABSTRACTRadiochemotherapy represents one of the greatest achievements in cancer treatment in recent decades, although it involves significant toxicity for patients. Research developed recently in the molecular biology of cancer has enabled understanding of the genetic and molecular changes that determine malign cellular transformation, which has led to the identification of key molecules, converting them into molecular targets that have led to a revolution in radiobiological concepts of cellular response to radiations and radioresistance.The new agents against molecular targets possess greater specificity and less adverse effects, making them more attractive than chemotherapy for combination with radiotherapy. They can act by inhibiting intracellular transduction signals, modulating the cellular cycle, apoptosis or inhibiting angiogenesis. The effect of radiotherapy can be strengthened through inhibition of cellular repopulation, improvement of tumour oxygenation, redistribution of the cellular cycle, inhibition of invasion and metastasis, and increase of radiosensitivity. The available data support its efficacy and applicability in preclinical and clinical studies in different tumour models and open up a promising path in cancer treatment.

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Treatment of non-small cell lung cancer with intensity-modulated radiation therapy in combination with cetuximab: the NEAR protocol (NCT00115518)

Cited by 30 publications

References 16 publications

Monoclonal Antibodies: An Emerging Class of Therapeutics in Non Small Cell Lung Cancer

Monoclonal Antibodies: An Emerging Class of Therapeutics in Non Small Cell Lung Cancer

Chemoradiation therapy in nonsmall cell lung cancer

Interaction of radiotherapy and new agents with molecular targets

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