Gefitinib is active in patients with brain metastases from non-small cell lung cancer and response is related to skin toxicity

Chiu, Chao‐Hua; Tsai, Chun‐Ming; Chen, Yuh‐Min; Chiang, Shu-Chen; Liou, Jer-Young; Perng, Reury-Perng

doi:10.1016/j.lungcan.2004.05.014

Cited by 129 publications

(76 citation statements)

References 29 publications

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“…In two phase II trials, IDEAL 1 and IDEAL 2 (10,11), gefitinib was shown to have substantial effect when used alone as salvage treatment for patients treated previously with chemotherapy. In Taiwan, where Chinese descendants represent a major proportion of the population, we have shown previously a tumor response rate of 33% (12). This outcome was higher than that observed in Caucasian patients but similar to that of Japanese patients (10,11).…”

supporting

confidence: 58%

“…Cell type, mutation status of EGFR, and performance status but not the number of prior chemotherapy regimen was associated with gefitinib response of NCSLC patients (12). When compared with currently available front-line chemotherapy, gefitinib showed much higher treatment efficacy in adenocarcinomas with EGFR mutations (85%) and comparable efficacy in adenocarcinomas with no EGFR mutations (f40%).…”

Section: Discussionmentioning

confidence: 93%

“…However, accumulated clinical evidence strongly suggests that ethnic/geographic factors play an important role in the response of patients to gefitinib treatment. This is based on the high response rates reported exclusively from countries in the Asia Pacific region, including Taiwan (12,20,21). Although the similarity of high response rates (f30%) among each independent group in this region was quite convincing, most of these data came from observational studies with no supporting molecular analyses.…”

Section: Discussionmentioning

confidence: 99%

“…Pretreatment staging, treatment response, and adverse events were evaluated as described previously (12). Clinical results of the first 76 patients from this study have been published.…”

Section: Methodsmentioning

confidence: 99%

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Mutation in the Tyrosine Kinase Domain of Epidermal Growth Factor Receptor Is a Predictive and Prognostic Factor for Gefitinib Treatment in Patients with Non–Small Cell Lung Cancer

Chou

Chiu²,

Li³

et al. 2005

Clinical Cancer Research

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Purpose: Mutations in epidermal growth factor receptor (EGFR) can be used to predict the tumor response of patients receiving gefitinib for non^small cell lung cancer (NSCLC).We investigated the association between mutations in EGFR tyrosine kinase domain and tumor response and survival in gefitinib-treated NSCLC patients. Experimental Design: EGFR mutations in exons 18 to 21were analyzed by DNA sequencing of paraffin-embedded tumor tissues from gefitinib-treated NSCLC patients. The results were correlated with clinical variables. Results: EGFR mutations were found in 61.1% (33 of 54) of cases; response rate and disease control rate were 56.8% and 68.5%, respectively. There was no significant difference in mutation rates between adenocarcinoma (29 of 43) and nonadenocarcinoma (4 of 11; P = 0.085). However, all four nonadenocarcinomas with EGFR mutations had no response to gefitinib. Presence of EGFR mutations was the only independent predictor for disease control (P = 0.003) and tumor response (P = 0.017) in multivariate analysis; positive predictive values were 87.9% and 70.8% and negative predictive values were 61.9% and 69.2%, respectively. In comparison with patients whose tumor was negative for EGFR mutations, patients with EGFR mutations had better progression-free survival (median, 7.6 versus 1.7 months; P = 0.011) and overall survival (median, 14.7 versus 4.7 months; P = 0.046). Conclusions: Mutations in EGFR tyrosine kinase correlate with treatment response and survival in gefitinib-treated NSCLC patients and can be used as a predictive and prognostic factor. Thus, analysis of EGFR tyrosine kinase mutations in lung adenocarcinoma is of clinical significance, as it can permit the customization of treatment with EGFR tyrosine kinase inhibitors.

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supporting

confidence: 58%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

“…Pretreatment staging, treatment response, and adverse events were evaluated as described previously (12). Clinical results of the first 76 patients from this study have been published.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Mutation in the Tyrosine Kinase Domain of Epidermal Growth Factor Receptor Is a Predictive and Prognostic Factor for Gefitinib Treatment in Patients with Non–Small Cell Lung Cancer

Chou

Chiu²,

Li³

et al. 2005

Clinical Cancer Research

Self Cite

289

169

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“…Finally, the tumor clone that metastasizes to the CNS may have molecular and genotypic alterations that render brain metastases more resistant. Despite these limitations, a number of drugs have been studied or reported with some success, most often in patients with recurrent brain metastases after standard therapy (Table 3 [45][46][47][48][49][50][51][52][53][54][55][56][57] ).…”

Section: Chemotherapymentioning

confidence: 99%

Current Management of Metastatic Brain Disease

Ranjan

Abrey

2009

Neurotherapeutics

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Summary: Brain metastases are the most common intracranial tumor in adults. The incidence of metastases is thought to be rising due to better detection and treatment of systemic malignancy. More widespread use and improved quality of MRI may lead to early detection of brain metastases. Available evidence suggests that survival is longer and quality of life improved if brain metastases are treated aggressively. This article reviews current therapeutic management used for brain metastases. To select the appropriate therapy, the physician must consider the extent of the systemic disease, primary histology, and patient age and performance status, as well as the number, size, and location of the brain metastases. Available treatment options include whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), surgery, and chemotherapy. Multidisciplinary approaches such as the combination of WBRT with SRS or surgery have shown superior results in terms of survival time, neurocognitive function, and quality of life. The utility and optimal use of chemotherapy and radiosensitizing agents is less clear. It is hoped that further advances and multidisciplinary approaches currently under study will result in improved patient outcomes. Key Words: Brain metastases, brain metastasis chemotherapy, brain metastasis radiotherapy, metastatic brain tumor, brain neoplasm.

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Brain Metastases

Tsao

2013

Radiation Oncology in Palliative Cancer Care

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Gefitinib is active in patients with brain metastases from non-small cell lung cancer and response is related to skin toxicity

Cited by 129 publications

References 29 publications

Mutation in the Tyrosine Kinase Domain of Epidermal Growth Factor Receptor Is a Predictive and Prognostic Factor for Gefitinib Treatment in Patients with Non–Small Cell Lung Cancer

Mutation in the Tyrosine Kinase Domain of Epidermal Growth Factor Receptor Is a Predictive and Prognostic Factor for Gefitinib Treatment in Patients with Non–Small Cell Lung Cancer

Current Management of Metastatic Brain Disease

Brain Metastases

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