Erlotinib with pemetrexed/cisplatin for patients with EGFR wild-type lung adenocarcinoma with brain metastases

Zhang, Yalei; Yang, Huanming; Yang, Xinyun; Deng, Qiuhua; Zhao, Meilin; Xu, Xin; He, Jianxing

doi:10.3892/mco.2014.256

Cited by 3 publications

(2 citation statements)

References 22 publications

(21 reference statements)

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“…Zhang et al (49) reported that some patients with advanced NSCLC with wild-type EGFR could benefit from the combination therapy of EGFR-TKI and platinum-based drugs. The present results suggested that the combination effects of gefitinib and cisplatin in H1299 and A549 varied, despite both cells containing wild-type EGFR.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, it was speculated that wild-type EGFR could not be used as a single biomarker to predict the combined effect of cisplatin and gefitinib. Hierarchical analyses of most previous clinical trials are based on EGFR genotype, which may explain the contradictory conclusions from the literature (9,14,15,49). Moreover, the biological difference of tumors may cause this inconsistency.…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of DNA‑PK by gefitinib causes synergism between gefitinib and cisplatin in NSCLC

Chi

Duan

et al. 2020

Int J Oncol

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Lung cancer has the highest incidence and mortality rates among the malignant tumor types worldwide. Platinum-based chemotherapy is the main treatment for advanced non-small-cell lung cancer (NSCLC), and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have greatly improved the survival of patients with EGFR-sensitive mutations. However, there is no standard therapy for treating patients who are EGFR-TKI resistant. Combining EGFR-TKIs and platinum-based chemotherapy is the most popular strategy in the clinical practice. However, the synergistic mechanism between EGFR-TKIs and platinum remains unknown. Therefore, the aim of the present study was to determine the synergistic mechanism of gefitinib (an EGFR-TKI) and cisplatin (a main platinum-based drug). MTT assay, apoptosis analysis, tumorsphere formation and an orthotropic xenograft mouse model were used to examine the combination effects of gefitinib and cisplatin on NSCLC. Co-immunoprecipitation and immunofluorescence were used to identify the underlying mechanism. It was found that gefitinib could selectively inhibit EGFR from entering the nucleus, decrease DNA-PK activity and enhance the cytotoxicity of cisplatin on NSCLC. Collectively, the results suggested that inhibition of DNA-dependent protein kinase by gefitinib may be due to the synergistic mechanism between gefitinib and cisplatin. Thus, the present study provides a novel insight into potential biomarkers for the selection of combination therapy of gefitinib and cisplatin.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhibition of DNA‑PK by gefitinib causes synergism between gefitinib and cisplatin in NSCLC

Chi

Duan

et al. 2020

Int J Oncol

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Oral Targeted Therapies and Central Nervous System (CNS) Metastases

et al. 2015

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The purpose of our review is to summarize the clinical activity of oral targeted agents against brain metastases. This includes BRAF inhibitors (dabrafenib and vemurafenib), human epidermal growth factor receptor inhibitors (lapatinib, gefitinib, erlotinib, and afatinib), multi-kinase angiogenesis inhibitors (sorafenib, sunitinib, pazopanib, and vandetanib), and ALK/c-MET (crizotinib) and ALK/IGF-1 (ceritinib) inhibitors. Effective systemic therapies are needed for long-term benefit in brain metastases and documentation of intracranial activity for many therapies is poor. Our review provides a summary of the literature with pertinent data for clinicians. This is needed as subjects with brain metastases are often prevented from enrolling in clinical trials and investigations focused on systemic therapies for brain metastases are rare.

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First-line pemetrexed and carboplatin plus anlotinib for epidermal growth factor receptor wild-type and anaplastic lymphoma kinase-negative lung adenocarcinoma with brain metastasis

Zhang

Kong

et al. 2020

Medicine

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Rationale: Brain metastasis (BM) is a serious complication in non-small cell lung cancer (NSCLC) patients. Pemetrexed is one of the preferred agents in nonsquamous NSCLC with BM; however, the traditional chemotherapy demonstrated limited efficacy partly due to drug resistance and the blood-brain barrier. Patient concerns: A 52-year-old male non-smoker was admitted for irritating cough, chest distress, and back pain. Diagnoses: Epidermal growth factor receptor wild-type, anaplastic lymphoma kinase-negative primary lung adenocarcinoma with an asymptomatic solitary BM (cTxNxM1b, IVA). Interventions: Pemetrexed (500 mg/m 2 of body surface area) and carboplatin (area under the curve of 5) were firstly administered every 3 weeks for 3 cycles, followed by pemetrexed/carboplatin plus anlotinib (12 mg daily; 2 weeks on and 1 week off) for another 3 cycles. Then maintenance anlotinib monotherapy was continued for a year, without unacceptable adverse events. Outcomes: The BM was slightly enlarged after 3 cycles of pemetrexed/carboplatin; however, a complete remission was achieved after the combination therapy. His intracranial progression-free survival was more than 2 years. Lessons: Pemetrexed/carboplatin plus anlotinib could be considered for the treatment of epidermal growth factor receptor wild-type, anaplastic lymphoma kinase-negative lung adenocarcinoma with BM. Further well-designed trials are warranted to verify this occasional finding.

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Erlotinib with pemetrexed/cisplatin for patients with EGFR wild-type lung adenocarcinoma with brain metastases

Cited by 3 publications

References 22 publications

Inhibition of DNA‑PK by gefitinib causes synergism between gefitinib and cisplatin in NSCLC

Inhibition of DNA‑PK by gefitinib causes synergism between gefitinib and cisplatin in NSCLC

Oral Targeted Therapies and Central Nervous System (CNS) Metastases

First-line pemetrexed and carboplatin plus anlotinib for epidermal growth factor receptor wild-type and anaplastic lymphoma kinase-negative lung adenocarcinoma with brain metastasis

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