Prospective Assessment of Pemetrexed or Pemetrexed Plus Platinum in Combination With Gefitinib or Erlotinib in Patients With Acquired Resistance to Gefitinib or Erlotinib: A Phase II Exploratory and Preliminary Study

Yu, Shaomin; Zhang, Bin; Xiang, Chengcheng; Shu, Yongqian; Wu, Hao; Huang, Xiang; Yin, Yongmei; Guo, Renhua

doi:10.1016/j.cllc.2014.09.007

Cited by 8 publications

(2 citation statements)

References 47 publications

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“…In a clinical setting, erlotinib treatment was approved for the treatment of NSCLC in 2004. However, the emerging clinical experience has disappointingly revealed that despite erlotinib demonstrating some antitumor activity in NSCLC, there is a high level of de novo resistance to such treatment [8]. Moreover, erlotinib has been shown to be ineffective for the majority of NSCLC patients because the patients are initially resistant to the inhibitor [9].…”

Section: Introductionmentioning

confidence: 99%

Synergistic Induction of Erlotinib-Mediated Apoptosis by Resveratrol in Human Non-Small-Cell Lung Cancer Cells by Down-Regulating Survivin and Up-Regulating PUMA

Nie

Hu²,

Zhang

et al. 2015

Cell Physiol Biochem

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Background/Aim: Treatment of human non-small-cell lung cancer (NSCLC) often involves uses of multiple therapeutic strategies with different mechanisms of action. Here we found that resveratrol (RV) enhanced the anti-tumor effects of epidermal growth factor receptor (EGFR) inhibitor erlotinib in NSCLC cells. Methods: Cell viability was measured by MTT assay and clonogenicity assay. Western blot was applied to assess the protein expression levels of target genes. Cell apoptosis was monitored by AnnexinV-FITC assay and sub-G1 population assay. Intracellular ROS were measured by flow cytometric analysis. Cell caspase activities were carried out by fluorometric assays. Results: Exposure of H460, A549, PC-9 and H1975 cells to minimal or non-toxic concentrations of RV and erlotinib synergistically reduced cell viability, colony formation and induced cell apoptosis. Furthermore, RV synergistically enhanced erlotinib-induced apoptosis was involved in ROS production. Additionally, co-treatment with RV and erlotinib repressed the expressions of anti-apoptosis proteins, such as survivin and Mcl-1, whereas promoted p53 and PUMA expression and caspase 3 activity. Moreover, the combination was also more effective at inhibiting the AKT/mTOR/S6 kinase pathway. Subsequently, small interfering RNA (siRNA) depletion of PUMA and overexpression of survivin significantly attenuated NSCLC cells apoptosis induced by the combination of the two drugs. Conclusion: Our findings suggested that RV synergistically enhanced the anti-tumor effects of erlotinib in NSCLC cells were involved in decrease of survivin expression and induction of PUMA expression. In conclusion, based on the observations from our study, we indicated that the combined administration of these two drugs might be considered as a novel therapeutic regimen for treating NSCLC.

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Section: Introductionmentioning

confidence: 99%

Synergistic Induction of Erlotinib-Mediated Apoptosis by Resveratrol in Human Non-Small-Cell Lung Cancer Cells by Down-Regulating Survivin and Up-Regulating PUMA

Nie

Hu²,

Zhang

et al. 2015

Cell Physiol Biochem

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“…The inclusion criteria for eligible patients were: histologically or cytologically confirmed NS-NSCLC according to the World Health Organization criteria [12] ; stage III or IV [13] ; wild-type epidermal growth factor receptor (EGFR); age ≥70 year; at least 1 measurable lesion; Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 to 2 [14] ; adequate organ function according to the results of routine blood test, [15] and normal electrocardiogram; expected survival time ≥3 months; pemetrexed chemotherapy cycles ≥2; adequate cancer tissue could be obtained for assessing the expression level of TS. Exclusion criteria: brain metastases; spinal metastasis and pancoast which needed radiotherapy first.…”

Section: Methodsmentioning

confidence: 99%

Single pemetrexed is noninferior to platinum-based pemetrexed doublet as first-line treatment on elderly Chinese patients with advanced nonsquamous nonsmall cell lung cancer

et al. 2017

Medicine

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Background:To evaluate the clinical efficacy and toxicity of single pemetrexed treatment compared with platinum-based pemetrexed doublet pemetrexed-based as first-line treatment for advanced nonsquamous nonsmall cell lung cancer (NS-NSCLC) in elderly Chinese patients.Methods:The study retrospectively reviewed 175 elderly Chinese patients with NS-NSCLC from June 2010 to September 2013: 90 patients received single pemetrexed treatment, 45 received pemetrexed plus oxaliplatin, and 40 received pemetrexed plus carboplatin. Clinical efficacy was assessed using disease control rate (DCR), overall survival (OS), and progression-free survival (PFS).Results:DCR, OS, and PFS did not significantly differ between single pemetrexed treatment (OS: 14.9 months; DCR: 62.2%; PFS: 3.3 months), pemetrexed plus oxaliplatin (OS: 16.5 months; DCR: 71.1%; PFS: 4.5 months), and pemetrexed plus carboplatin (OS: 15.5 months; DCR: 70.0%; PFS: 4.6 months) groups. Pemetrexed treatment caused significantly lower incidences of adverse events, such as hepatotoxicity and peripheral nerve injury. Performance status (PS), TNM stage, and Thymidylate synthase (TS) expression were predictive factors of DCR. Pemetrexed chemotherapy cycles, PS, and TNM stage were independent prognostic factors.Conclusions:Single pemetrexed was noninferior to platinum-based pemetrexed doublet for clinical efficacy and safety in elderly Chinese patients with advanced NS-NSCLC. Chemotherapy cycles, performance status, and TNM stage were independent prognostic factors.

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Intercalated Chemotherapy and Epidermal Growth Factor Receptor Inhibitors for Patients With Advanced Non–Small-cell Lung Cancer: A Systematic Review and Meta-analysis

Salvia

Rossi

Galetta

et al. 2017

Clinical Lung Cancer

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Prospective Assessment of Pemetrexed or Pemetrexed Plus Platinum in Combination With Gefitinib or Erlotinib in Patients With Acquired Resistance to Gefitinib or Erlotinib: A Phase II Exploratory and Preliminary Study

Cited by 8 publications

References 47 publications

Synergistic Induction of Erlotinib-Mediated Apoptosis by Resveratrol in Human Non-Small-Cell Lung Cancer Cells by Down-Regulating Survivin and Up-Regulating PUMA

Synergistic Induction of Erlotinib-Mediated Apoptosis by Resveratrol in Human Non-Small-Cell Lung Cancer Cells by Down-Regulating Survivin and Up-Regulating PUMA

Single pemetrexed is noninferior to platinum-based pemetrexed doublet as first-line treatment on elderly Chinese patients with advanced nonsquamous nonsmall cell lung cancer

Intercalated Chemotherapy and Epidermal Growth Factor Receptor Inhibitors for Patients With Advanced Non–Small-cell Lung Cancer: A Systematic Review and Meta-analysis

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