Gefitinib as palliative therapy for lung adenocarcinoma metastatic to the brain

Wu, Chi-Fang; Li, Yun Long; Wang, Zhao Meng; Li, Zhang; Zhang, Tong Xiao; Zhong, Wei

doi:10.1016/j.lungcan.2007.03.011

Cited by 128 publications

(85 citation statements)

References 22 publications

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“…The response rate in patients with brain metastases is reportedly similar to that in patients with NSCLC (Wu et al 2007). On the other hand, only case reports of carcinomatous meningitis have been published, probably because of the small number of carcinomatous meningitis cases treated with gefitinib (Namba et al 2004;Kim et al 2005;Sakai et al 2006).…”

Section: Discussionmentioning

confidence: 61%

“…The effects of gefitinib on metastatic lesions in the central nervous system have been reported (Namba et al 2004;Kim et al 2005;Sakai et al 2006;Wu et al 2007). The response rate in patients with brain metastases is reportedly similar to that in patients with NSCLC (Wu et al 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Gefitinib has significant anti-tumor activity against NSCLC, with a response rate of 10-30%, and several recent reports have shown that gefitinib treatment is effective against brain metastases and carcinomatous meningitis (Namba et al 2004;Kim et al 2005;Sakai et al 2006;Wu et al 2007). Here, we present a case of meningeal metastasis successfully treated with gefitinib and WBI, and we report the patient's cerebrospinal fluid (CSF) and serum levels of gefitinib.…”

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confidence: 99%

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Successful Treatment of Carcinomatous Meningitis with Gefitinib in a Patient with Lung Adenocarcinoma Harboring a Mutated EGF Receptor Gene

Fukuhara

Saijo

Sakakibara

et al. 2008

Tohoku J. Exp. Med.

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Carcinomatous meningitis is a severe complication of lung cancer. Although treatment with gefitinib, a tyrosine kinase inhibitor of epidermal growth factor (EGF) receptor, has been reported to be highly effective against lung cancers harboring a mutated EGF gene, its effect against carcinomatous meningitis is unknown. Here, we report successful treatment of carcinomatous meningitis with gefitinib in a lung cancer patient suffered from meningeal metastasis. A 62-year-old, non-smoking, Japanese male was admitted for headache, failing vision, and temporary loss of consciousness and was subsequently diagnosed with stage IV lung adenocarcinoma and carcinomatous meningitis. A tumor sample revealed the in-frame deletion of codons 746 to 750 (E746 to A750) in exon 19 of the EGF gene, which leads to constitutive activation of the tyrosine kinase domain and high-affinity binding of gefitinib. The patient's performance status was poor owing to progression of the meningitis and elevated cerebrospinal fluid (CSF) pressure. Combined treatment with gefitinib (250 mg/day) and whole-brain irradiation (36 Gray total) proved to be effective. It is noteworthy that the level of gefitinib in the CSF was less than 1% of the serum level (serum: 117 nM before drug re-administration and 132 nM 2 hrs later; CSF: 0.9 nM both before and 2 hrs after drug re-administration). Gefitinib treatment should be considered for patients with carcinomatous meningitis and lung adenocarcinoma harboring a mutated EGF gene. carcinomatous meningitis; EGF; EGF-TKI; gefitinib; lung cancer. Metastases to the central nervous system, which are often observed in cases of non-small cell lung cancer (NSCLC), result in poor performance status of the patient. Although brain metastases can be controlled by whole-brain irradiation (WBI) or γ -knife irradiation, leptomenin-

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Successful Treatment of Carcinomatous Meningitis with Gefitinib in a Patient with Lung Adenocarcinoma Harboring a Mutated EGF Receptor Gene

Fukuhara

Saijo

Sakakibara

et al. 2008

Tohoku J. Exp. Med.

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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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“…Phase II studies of gefitinib on brain metastases from NSCLC indicated objective responses occur in 33% of patients (Asia) (32,33) Table I. Front-line chemotherapy for non-small cell lung cancer.…”

Section: Second-line Chemotherapy Epidermal Growth Factor Receptor Tymentioning

confidence: 99%

Medical management of brain metastases from lung cancer (Review)

Yamanaka¹

2009

Oncol Rep

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Abstract. Brain metastases are a frequent complication in patients with lung cancer and a significant cause of morbidity and mortality. The prognosis of these patients is poor. Medical therapies for brain metastases are neither wellstudied nor established. This review analyzes the impact of medical treatment on survival by reviewing recent articles of the management of brain metastases from lung cancer patients. Chemotherapy for brain metastases from lung cancer is effective for both small cell and non-small cell lung cancer. Since brain metastases are part of systemic progression, chemotherapy should always be considered for the therapeutic management of brain metastases. Available data and response rates in lung cancer patients indicated that medical treatment for the management of brain metastases should be part of a multimodality treatment.

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Gefitinib as palliative therapy for lung adenocarcinoma metastatic to the brain

Cited by 128 publications

References 22 publications

Successful Treatment of Carcinomatous Meningitis with Gefitinib in a Patient with Lung Adenocarcinoma Harboring a Mutated EGF Receptor Gene

Successful Treatment of Carcinomatous Meningitis with Gefitinib in a Patient with Lung Adenocarcinoma Harboring a Mutated EGF Receptor Gene

Current Management of Metastatic Brain Disease

Medical management of brain metastases from lung cancer (Review)

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