Lung cancer

Giaccone, Giuseppe; Smit, Egbert F.

doi:10.1016/s0921-4410(03)21022-x

Cited by 5 publications

(2 citation statements)

References 199 publications

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“…For advanced NSCLC, platinum‐based chemotherapy as a standard treatment achieves at best partial response in only approximately 30% of patients and a modest increase in survival 2,3 . The survival rate at 1 year after first‐line chemotherapy is around 30–40% with 8–10 months median survival 4 . These treatments are associated with considerable toxicity, particularly myelosuppression, and thus more effective and less toxic treatments are clearly needed for advanced NSCLC.…”

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Epidermal growth factor receptor mutations in lung cancers

Yatabe¹,

Mitsudomi

2007

Pathology International

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In 2004, two groups reported somatic mutations in the gene for the epidermal growth factor receptor (EGFR) in patients with non-small cell lung cancer (NSCLC), which were highly correlated with the clinical response to the anticancer drug, gefitinib. Since then, a tremendous amount of knowledge has accumulated, and sheds light on significant oncological properties as well as the clinical relevance of this mutation, which could be applicable to other malignancies. The EGFR mutations are distributed throughout the kinase domain, but a deletion in exon 19 and the point mutation L858R in exon 21 account for approximately 90%, which confer a greater response to gefitinib treatment, compared with other types of EGFR mutations. These EGFR mutations in the tyrosine kinase domain are seldom acquired in cancers of the other organs and the mutations preferentially involve a subset of lung cancers, which are clinicopathologically characterized by female sex, non-smoking, adenocarcinoma histology and East Asian ethnicity. In Japan, the EGFR mutations are detected in approximately 30% of overall NSCLC and approximately 40% of surgically resected adenocarcinomas. The morphological features of adenocarcinomas harboring the mutations were reported to be frequent in those with bronchioloalveolar features, but it is suggested that the cellular lineage of the putative original cells of the cancers refines the subset more clearly. In the present study the current knowledge of EGFR mutations is reviewed, insights from which raise many further questions, and thus suggest new directions for future research.

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confidence: 99%

“…2,3 The survival rate at 1 year after first-line chemotherapy is around 30-40% with 8-10 months median survival. 4 These treatments are associated with considerable toxicity, particularly myelosuppression, and thus more effective and less toxic treatments are clearly needed for advanced NSCLC.…”

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confidence: 99%

Epidermal growth factor receptor mutations in lung cancers

Yatabe¹,

Mitsudomi

2007

Pathology International

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Roles of Mutation and Epimutation in the Development of Lung Disease

Coleman

2008

Molecular Pathology Library

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Erlotinib for Frontline Treatment of Advanced Non–Small Cell Lung Cancer: a Phase II Study

Giaccone¹,

Ruiz²,

Chevalier

et al. 2006

Clinical Cancer Research

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183

130

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Purpose: Erlotinib has proven activity in pretreated patients with advanced non–small cell lung cancer (NSCLC). We evaluated erlotinib in the frontline treatment of advanced NSCLC and assessed biological predictors of outcome. Experimental Design: In this phase II study, chemotherapy-naive patients with stage IIIB/IV NSCLC received oral erlotinib (150 mg/d) until disease progression or unacceptable toxicity occurred. Tumor response was assessed every 6 weeks, and samples were analyzed for potential molecular markers of treatment response and survival. The primary end point was the proportion of patients without disease progression after 6 weeks of treatment. Results: Fifty-three patients were eligible. The overall rate of nonprogression at 6 weeks was 52.8% (28 of 53 patients). Tumor response rate was 22.7%, with 1 complete response, 11 partial responses, and 16 cases of stable disease. Responses were seen across most patient clinical characteristics. The median duration of tumor response was 333 days; median overall survival was 391 days; and median time to disease progression was 84 days. Erlotinib was well tolerated, the main treatment-related adverse events being mild-to-moderate rash and diarrhea. Histologic material for biological studies was available in 29 cases. Four of five responders and one patient with stable disease had a classic epidermal growth factor receptor tyrosine kinase mutation. Two progressing patients exhibited epidermal growth factor receptor point mutations (one with T790M mutation), and K-ras mutations were detected in 10 nonresponders. Conclusions: Erlotinib shows significant antitumor activity in the first-line treatment of advanced NSCLC and may be a viable alternative to chemotherapy. Patient selection cannot easily be based on clinical or biological variables.

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Lung cancer

Cited by 5 publications

References 199 publications

Epidermal growth factor receptor mutations in lung cancers

Epidermal growth factor receptor mutations in lung cancers

Roles of Mutation and Epimutation in the Development of Lung Disease

Erlotinib for Frontline Treatment of Advanced Non–Small Cell Lung Cancer: a Phase II Study

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