Phase II Study of Cetuximab in Combination With Chemoradiation in Patients With Stage IIIA/B Non–Small-Cell Lung Cancer: RTOG 0324

Blumenschein, George R.; Paulus, Rebecca; Curran, Walter J.; Robert, Francisco; Fossella, Frank V.; Werner‐Wasik, Maria; Herbst, Roy S.; Doescher, P.; Choy, Hak; Komaki, Ritsuko

doi:10.1200/jco.2010.31.7875

Cited by 149 publications

(85 citation statements)

References 29 publications

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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: 54%

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: 54%

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

Guilleminault¹,

Lemarié²,

Heuzé-Vourc’h³

2012

JCT

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“…RTOG 0324 evaluated the role of cetuximab in combination with chemoradiotherapy for locoregionally advanced stage IIIA/B NSCLC. 114 This combination of cetuximab with chemoradiotherapy was shown to be feasible and demonstrated promising results with response rate of 62%, median survival of 22.7 months, and 24-month overall survival rate of 49.3% The median and overall survival achieved with this regimen were longer than any previously reported by the RTOG. And, consequently, this regimen is currently being tested in a phase III trial (results of which are not yet available).…”

Section: Unresectable Diseasementioning

confidence: 53%

Molecular Profiling in Non–Small Cell Lung Cancer: A Step Toward Personalized Medicine

Raparia

Villa

DeCamp

et al. 2013

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Lung carcinoma is the result of sequential accumulation of genetic and epigenetic changes. Lung adenocarcinoma is a heterogeneous disease with diverse somatic mutations, and several of them include the socalled driver mutations, which may serve as ''druggable'' therapeutic targets. Thus, development of personalized approaches for the treatment of non-small cell lung carcinoma (NSCLC) mandates that pathologists make a precise histologic classification inclusive of routine molecular analysis of such tumors.Objective.-To address the molecular mechanisms underlying NSCLC and how this knowledge reflects the multidisciplinary approach in the diagnosis and management of these patients. We will also summarize the current available and investigational personalized therapies for patients with resectable early-stage, unresectable locally advanced, and metastatic NSCLC.Data Sources.-Peer-reviewed published literature and personal experience.Conclusions.-There are multiple mechanisms involved in the pathogenesis of lung cancer, which operate in parallel and involve pathways of activation and inhibition of various cellular events. Further research is essential to characterize the histologic and mutational profiles of lung carcinomas, which will ultimately translate into improved and more personalized therapeutic management of patients with lung cancer.(Arch Pathol Lab Med. 2013;137:481-491; doi: 10.5858/ arpa.2012-0287-RA) L ung cancer is the leading cause of cancer-related mortality in both men and women in the United States. It is projected that in 2012, lung cancer will account for 26% and 29% of cancer-related deaths in the female and male population, respectively.1 Historically, lung cancer has been divided into 2 major categories based on the histologic features and response to conventional therapies, and they include non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma. NSCLC includes 3 cell types (adenocarcinoma, squamous cell carcinoma, and large cell carcinoma), and these can be further divided into various subtypes or variants.2 NSCLC accounts for most (~80%) of the lung cancers, with lung adenocarcinoma being the most common subtype in the United States. Despite significant improvements in radiologic imaging, supportive care, availability of newer antineoplastic agents, and multimodality therapy, the 5-year relative survival rate for lung cancer in the United States remains dismal, that is, at only 16% in 2007 compared to 12% in 1975, thus indicating little improvement in survival rate over a period of 3 decades.

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“…Em recente metanálise 11 , observou-se que, até aquele momento, se considerados todos os estudos de fase I, I/II ou II nos quais havia o emprego de terapia-alvo com RQT em pacientes com NPNPC localmente avançada [12][13][14][15][16][17][18] , quando os resultados eram comparados com o tratamento-padrão, os pacientes não apresentavam melhora clinicamente relevante, como sobrevida livre de doença ou sobrevida global. Apresentavam, no entanto, aumento estatisticamente significativo do nível de efeitos secundários graves (grau III a V) 19 durante o tratamento -o que é bastante preocupante, já que esses pacientes tinham, no momento do estudo, diagnós-tico de enfermidade com potencial curativo.…”

Section: Conflito De Interesses Em Ensaios Clínicos Iniciais Envolvenunclassified

“…A metanálise reuniu um total de sete ensaios clínicos de fase I/II realizados nos Estados Unidos e em países europeus, durante o período de 2000 a 2011, empregando terapia-alvo e RQT, em pacientes com NPNPC localmente avançada [12][13][14][15][16][17][18] . As conclusões apresentadas foram então classificadas, pelos autores do presente estudo, em favorável, desfavorável ou neutra em relação à terapia-alvo testada, de acordo com a recomendação (ou não) da utilização da droga em ensaios clínicos posteriores ou, eventualmente, na prá-tica clínica cotidiana, posteriormente ao estudo.…”

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Conflito de interesses em ensaios clínicos iniciais envolvendo pacientes com neoplasia de pulmão

Santos¹,

Silva²,

Paranhos

2014

Rev. Bioét.

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ResumoO tratamento padrão para neoplasia de pulmão de não pequenas células (NPNPC) localmente avançada é radioquimioterapia (RQT). Resultados insatisfatórios de sobrevida estimularam estudos iniciais com drogasalvo. O presente trabalho analisou conflitos de interesse envolvidos em ensaios clínicos fase I/II utilizando-se terapia-alvo + RQT, em pacientes com NPNPC localmente avançada, com base em metanálise apresentada anteriormente. A sobrevida alcançada não demonstrou diferença estatística, comparada ao tratamento-padrão. No entanto, houve aumento da toxicidade. Além disso, 85,7% dos estudos registraram existência de conflitos de interesses. Avaliou-se que o financiamento, pela indústria farmacêutica, está associado a conclusões favoráveis ao tratamento testado. Conforme a DUBDH, benefícios devem ser maximizados e qualquer dano possível, minimizado. E, no entanto, pacientes com enfermidade potencialmente curável, submetendo-se a estudos frequentemente patrocinados pela indústria, apresentaram qualidade de vida diminuída. A conclusão desses estudos, possivelmente influenciada pelos conflitos de interesses dos pesquisadores, está frequentemente distanciada da realidade. Palavras-chave: Conflito de interesses. Medição de risco. Pesquisa biomédica-risco. Resumen Conflicto de intereses en ensayos clínicos iniciales involucrando pacientes con neoplasia de pulmónEl tratamiento estándar para la neoplasia de pulmón de células no pequeñas (NPNPC) localmente avanzada es la radio quimioterapia (RQT). Resultados de supervivencia, todavía, insatisfactoria, han estimulado estudios iniciales con drogas blanco. El presente estudio ha examinado los conflictos de interés que influyen en ensayos clínicos de fase I/II utilizando la terapia blanco + RQT en pacientes con NPNPC localmente avanzada, basada en meta análisis presentada precedentemente. La supervivencia alcanzada no ha resultado en ninguna diferencia estadística si comparada con el tratamiento estándar. Sin embargo, se ha visto un aumento de la toxicidad. Y además, el 85,7% de los estudios han informado la existencia de conflictos de intereses. Se ve, entonces, que la financiación de la industria farmacéutica puede estar asociada con resultados favorables para el tratamiento probado. De acuerdo con la DUBDH, los beneficios deben ser maximizados y los posibles daños deben ser, minimizados. Y entre tanto, los pacientes con enfermedad potencialmente curable, que se someten a estudios a menudo patrocinados por la industria presentaron una disminución de la calidad de vida. La conclusión de estos estudios, posiblemente influenciada por los conflictos de intereses de los investigadores, se aleja, frecuentemente de la realidad. Palabras-clave: Conflicto de intereses. Medición de riesgo. Investigación biomédica-riesgo. Abstract Conflict of interests in initial clinical practice involving patients whith lung neoplasiaThe standard treatment for locally advanced non-small cell lung cancer (NSCLC) is radiochemotherapy (RCT). Unsatisfactory overall survival stimulated initial studies ...

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Phase II Study of Cetuximab in Combination With Chemoradiation in Patients With Stage IIIA/B Non–Small-Cell Lung Cancer: RTOG 0324

Cited by 149 publications

References 29 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

Molecular Profiling in Non–Small Cell Lung Cancer: A Step Toward Personalized Medicine

Conflito de interesses em ensaios clínicos iniciais envolvendo pacientes com neoplasia de pulmão

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