Safety profiles of non-small cell lung cancer patients treated with pemetrexed plus carboplatin: a real-world retrospective, observational, cohort study

Chen, Lei; Antonio, Belén San; Yan, Yu; Chen, Jian; Goodloe, Robert; John, William J.

doi:10.1080/03007995.2017.1297700

Cited by 3 publications

(2 citation statements)

References 26 publications

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“…All tissues were stored at -80°C and were confirmed as NSCLC. Inclusion criteria were as follows: (1) Patients diagnosed with NSCLC according to diagnostic standards [19] by cytologist or pathologist and were unable or unwilling to undergo surgery; (2) The age range was 18 - 75 years, the Karnofsky score was greater than 70, and the expected survival time was more than 6 months using an objective measurable lesion index. The routine blood parameters, liver, kidney functions and electrocardiographs (ECG) were normal prior to receiving treatment.…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-183 Acts as a Tumor Suppressor in Human Non-Small Cell Lung Cancer by Down-Regulating MTA1

Yang

Zheng

Yao

et al. 2018

Cell Physiol Biochem

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Backgrounds/Aims: MicroRNAs (miRs) often contribute to the progression of non-small cell lung cancer (NSCLC) via regulation of mRNAs that are involved in lung homeostasis. We conducted a study aimed at exploring the roles of miR-183 in the proliferation, epithelial-mesenchymal transition (EMT), invasion and migration of human NSCLC cells via targeting MTA1. Methods: NSCLC and adjacent normal tissues were collected from 194 patients with NSCLC. Positive expression of MTA1 protein was detected by immunohistochemistry. The highest levels of expression of miR-183 were detected using RT-qPCR in SPC-A-1 cells, which were selected and assigned to the following groups: blank, negative control (NC), miR-183 mimic, miR-183 inhibitor, siRNA-MTA1, and miR-183 inhibitor + siRNA-MTA1. The expression of miR-183 and the mRNA and protein expression of MTA1, E-cadherin, Vimentin, Snail, PCNA, Bax and Bcl-2 in tissues and transfected cells were measured using RT-qPCR and western blot analysis. Cell proliferation, apoptosis, migration and invasion were evaluated by CCK-8, flow cytometry, scratch tests and Transwell assays. Tumor xenografts were conducted in nude mice to determine tumor growth. Results: SPC-A-1 cells with the highest levels of miR-183 expression were selected. Compared with adjacent normal tissues, the expression of miR-183 and the mRNA and protein expression of E-cadherin and Bax were decreased in NSCLC tissues, while mRNA and protein expression of MTA1, Vimentin, snail, PCNA and Bcl-2 were increased. MiR-183 was over-expressed in the miR-183 mimic group and under-expressed in the miR-183 inhibitor and miR-183 inhibitor + siRNA-MTA1 groups. In the miR-183 mimic and siRNA-MTA1 groups, the mRNA and protein expression of E-cadherin and Bax, as well as cell apoptosis, were enhanced, while the expression levels of MTA1, Vimentin, snail, PCNA and Bcl-2 mRNA and protein, cell proliferation, migration, invasion and tumor growth were reduced relative to the blank and NC groups. The miR-183 inhibitor group exhibited an opposite trend. Conclusion: Our study indicates that miR-183 down-regulates MTA1 to inhibit the proliferation, EMT, migration and invasion of human NSCLC cells.

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Section: Methodsmentioning

confidence: 99%

MicroRNA-183 Acts as a Tumor Suppressor in Human Non-Small Cell Lung Cancer by Down-Regulating MTA1

Yang

Zheng

Yao

et al. 2018

Cell Physiol Biochem

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“…Therefore, chemotherapy is still indispensable (4)(5)(6). Some randomized controlled trials and real-world studies abroad demonstrated that pemetrexed-cisplatin induction and pemetrexed maintenance therapy is an effective and well-tolerated regimen in stage IIIB-IV patients with non-squamous NSCLC (7)(8)(9)(10)(11)(12)(13)(14), but there is still a lack of large sample size evidence to report the survival benefit of pemetrexed as the initial chemotherapy in Chinese patients with advanced lung adenocarcinoma.…”

Section: Introductionmentioning

confidence: 99%

Survival Benefit and Genetic Profile of Pemetrexed as Initial Chemotherapy in Selected Chinese Patients With Advanced Lung Adenocarcinoma

Guo

Zhang

et al. 2020

Front. Oncol.

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This study investigated survival in selected Chinese patients with advanced lung adenocarcinoma who received initial chemotherapy with pemetrexed. We also explored the relationship between genetic biomarkers and pemetrexed efficacy. Methods: We retrospectively collected patients (n = 1,047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed. Results: The median DOT was 9.1 months (95% CI: 8.5-9.8), and the median OS was 26.2 months (95% CI: 24.2-28.1). OS was positively correlated with DOT (r = 0.403, P < 0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), and PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT > 6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS, and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤ 6.9 months set. Conclusion: This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.

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Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies

Okamoto

Schuette

Stinchcombe

et al. 2017

Current Medical Research and Opinion

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Safety profiles of non-small cell lung cancer patients treated with pemetrexed plus carboplatin: a real-world retrospective, observational, cohort study

Abstract: Results from this real-world analysis add to existing evidence from randomized clinical trials about PCb safety profiles in the overall NSCLC population and in elderly patients. These results may guide physicians when making treatment decisions.

Cited by 3 publications

References 26 publications

MicroRNA-183 Acts as a Tumor Suppressor in Human Non-Small Cell Lung Cancer by Down-Regulating MTA1

MicroRNA-183 Acts as a Tumor Suppressor in Human Non-Small Cell Lung Cancer by Down-Regulating MTA1

Survival Benefit and Genetic Profile of Pemetrexed as Initial Chemotherapy in Selected Chinese Patients With Advanced Lung Adenocarcinoma

Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies

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