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International Journal of Oncology Jan 2016Because poor performance status (PS) is an independent prognostic factor in non-small cell lung cancer (NSCLC), PS scores are widely used by oncologists to make... (Review)
Review
Because poor performance status (PS) is an independent prognostic factor in non-small cell lung cancer (NSCLC), PS scores are widely used by oncologists to make treatment decisions. Advanced NSCLC patients with an Eastern Cooperative Oncology Group PS of 2 have poor prognoses and are frequently excluded from clinical trials. This article reviews the efficacy and safety of pemetrexed in this patient group. We identified English-language literature (through March 2015) involving completed and ongoing studies through searches of PubMed, meeting abstracts, ClinicalTrials.gov and the European Clinical Trials Register; search terms included 'pemetrexed,' 'NSCLC' and 'PS2'. Only studies reporting ≥1 subset analysis of PS2 patients receiving pemetrexed were chosen. Our search identified a total of ten pemetrexed studies in PS2 patients. Eight studies included only chemonaive patients, one study included both chemonaive patients and patients with one prior chemotherapy regimen and one study included only patients with one prior regimen. In subset analyses in these studies, PS2 patients had worse outcomes than PS0-1 patients regardless of treatment. In a phase 3 study, chemonaive advanced NSCLC patients with PS2 receiving pemetrexed‑carboplatin versus pemetrexed experienced improved overall survival [hazard ratio (HR)=0.62; P=0.001], progression-free survival (HR=0.46; P<0.001) and response (P=0.032). This review confirms the poorer outcomes in PS2 vs. PS0-1 patients. Although it is not an approved combination therapy, in clinical studies, PS2 patients treated with pemetrexed plus carboplatin as first-line therapy had improved response rates and survival. Additional research on PS2 patients is needed.
Topics: Carboplatin; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Humans; Kaplan-Meier Estimate; Karnofsky Performance Status; Pemetrexed; Treatment Outcome
PubMed: 26530033
DOI: 10.3892/ijo.2015.3219 -
Cellular Signalling Oct 2023Survivin is a bifunctional protein that plays crucial roles in tumorigenesis. In the present study, we discovered that the natural product gastrodin suppressed the cell...
Survivin is a bifunctional protein that plays crucial roles in tumorigenesis. In the present study, we discovered that the natural product gastrodin suppressed the cell viability and colony formation of non-small cell lung cancer (NSCLC) cell lines A549, HCC827, and H460 in a dose-dependent manner. In addition, gastrodin enhanced the protein levels of cleaved-caspase 3 by activating the endogenous mitochondrial apoptosis pathway. Gastrodin inhibits protein kinase B (Akt)/WEE1/cyclin-dependent kinase 1 (CDK1) signaling to downregulate survivin Thr34 phosphorylation. Survivin Thr34 dephosphorylation caused by gastrodin interfered with the binding of ubiquitin-specific protease 19 (USP19), which eventually destabilized survivin. We revealed that the growth of NSCLC xenograft tumors was markedly suppressed by gastrodin in vivo. Furthermore, gastrodin overcomes pemetrexed resistance in vivo or in vitro. Our results suggest that gastrodin is a potential antitumor agent by reducing survivin in NSCLC.
Topics: Humans; Survivin; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Pemetrexed; Apoptosis; Cell Line, Tumor; Cell Proliferation; Endopeptidases
PubMed: 37586466
DOI: 10.1016/j.cellsig.2023.110851 -
The Journal of Allergy and Clinical... Jan 2019
Topics: Adenocarcinoma of Lung; Allergens; Anaphylaxis; Antineoplastic Combined Chemotherapy Protocols; Cyanosis; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Dyspnea; Exanthema; Female; Histamine Release; Humans; Immunoglobulin E; Lung Neoplasms; Middle Aged; Neoplasm Staging; Pemetrexed; Skin Tests
PubMed: 29908333
DOI: 10.1016/j.jaip.2018.06.004 -
Drug Delivery and Translational Research Oct 2022Malignant pleural mesothelioma (MPM) is a rare malignancy with poor prognosis, for which chemotherapy with pemetrexed (PEM) is among the few clinical treatments. PEM...
Malignant pleural mesothelioma (MPM) is a rare malignancy with poor prognosis, for which chemotherapy with pemetrexed (PEM) is among the few clinical treatments. PEM suffers, however, fast clearance, moderate drug exposure, and dose-limiting toxicities. Here, we report on epidermal growth factor receptor (EGFR)-targeted disulfide-crosslinked biodegradable chimaeric polymersomes (EGFR-CPs) to firmly load PEM and boost chemotherapy of MPM. EGFR-CPs encapsulating 8.7-16.4 wt.% PEM (EGFR-CPs-PEM) showed diameters of 62-65 nm and reduction-responsive drug release property. EGFR-CPs-PEM was more efficiently taken up by EGFR-overexpressed MSTO-211H cells, inducing about 4.7-fold enhanced anticancer activity compared with non-targeted CPs-PEM control. Intriguingly, the in vivo experiments in MSTO-211H xenograft mouse model revealed that EGFR-CPs-PEM brought about superior tumor deposition and penetration to CPs-PEM, and significantly more potent tumor repression than CPs-PEM and free PEM. This polymersome-enabled EGFR-targeted delivery of PEM offers an appealing therapeutic strategy for MPM.
Topics: Animals; Cell Line, Tumor; ErbB Receptors; Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Mice; Pemetrexed
PubMed: 34802094
DOI: 10.1007/s13346-021-01094-2 -
Annales de Dermatologie Et de... Dec 2018Drug-induced eyelid edemas are rare. Herein, we describe a patient who developed this type of edema under chemotherapy.
BACKGROUND
Drug-induced eyelid edemas are rare. Herein, we describe a patient who developed this type of edema under chemotherapy.
PATIENTS AND METHODS
A 56-year-old male patient with a history of hypertension and adenocarcinoma of the lung with brain metastases consulted for incipient non-itchy eyelid edema with progressive worsening. The swelling occurred after 3 cycles of pemetrexed-carboplatin. There was no evidence of any other cause of edema. A diagnosis of pemetrexed-induced eyelid edema was made. Given the efficacy of this treatment and the patient's consent thereto, it was maintained.
DISCUSSION
Palpebral edemas secondary to pemetrexed are very rare, with only 22 published cases in the literature. Other differential diagnoses must be ruled out before considering this etiology. The pathogenesis of eyelid edema remains unknown. One hypothesis is capillary protein leakage inducing swelling in soft tissue and non-malignant effusion, as has been suggested for docetaxel. Other agents such as tyrosine kinase inhibitors (imatinib and nilotinib) and mTOR inhibitors (sirolimus) may also cause eyelid edema. Treatment of eyelid edema is difficult and one case of surgical treatment has been published with good results and no recurrence after 6 months.
Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carboplatin; Drug Eruptions; Edema; Eyelid Diseases; Fatal Outcome; Humans; Lung Neoplasms; Male; Middle Aged; Pemetrexed
PubMed: 30297200
DOI: 10.1016/j.annder.2018.07.023 -
Expert Opinion on Pharmacotherapy Dec 2018Non-small cell lung cancer (NSCLC) remains one of the big cancer killers, despite the introduction of a number of approved therapeutics in recent times. Pemetrexed is a... (Review)
Review
Non-small cell lung cancer (NSCLC) remains one of the big cancer killers, despite the introduction of a number of approved therapeutics in recent times. Pemetrexed is a multi-target folate inhibitor, which is currently available to patients affected by advanced non-squamous NSCLC in combination with a platinum derivate in first-line therapy and as a single agent in second-line therapy. Areas covered: This review covers presents the use pemetrexed in the management of NSCLC by exploring the data available from clinical trials and meta-analyses. Data from a phase III trial confirmed its role in the first-line setting in combination with immune checkpoint inhibitors (ICIs). Furthermore, data suggested a role for pemetrexed in local and advanced NSCLC. Expert opinion: To date, in spite of the introduction of novel anti-neoplastic agents, pemetrexed still represents a cornerstone in the management of non-squamous NSCLC. Furthermore, recently published data support its role in innovative combinations including together with chemotherapy and immunotherapy.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Folic Acid Antagonists; Humans; Lung Neoplasms; Pemetrexed
PubMed: 30354693
DOI: 10.1080/14656566.2018.1536746 -
Journal of Thoracic Oncology : Official... Sep 2021
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Pemetrexed
PubMed: 34242787
DOI: 10.1016/j.jtho.2021.06.021 -
European Journal of Clinical... May 2023Pemetrexed has shown efficacy as monotherapy or in combination with platinum salts in the treatment of non-small cell lung cancer and mesothelioma. However, severe...
PURPOSE
Pemetrexed has shown efficacy as monotherapy or in combination with platinum salts in the treatment of non-small cell lung cancer and mesothelioma. However, severe hematological toxicities induced by pemetrexed-based chemotherapy have been observed. Some studies have suggested that drug interactions may be associated with pemetrexed toxicity. The objective of this study was to determine predictive factors, including drug interactions, associated with pemetrexed toxicity.
METHODS
This retrospective open monocentric study included patients consecutively treated with pemetrexed after a multidisciplinary risk assessment. Patients who experienced toxicity of grade 3 or 4 according to the Common Terminology Criteria for Adverse Events v5.0, or a grade 2 leading to a change in management, during the first four courses of pemetrexed, were assigned to the early limiting toxicities (ELT) group. Univariate and multivariable logistic regression models were used to test the association variables with the occurrence of ELT.
RESULTS
Seventy-four patients were included in this study (median age: 67 years, with non-small cell lung cancer adenocarcinoma (88%), mesothelioma (7%), or others (5%). Thirty-six patients (49%) were assigned to the ELT group (27 grades 3 and 4; 9 grade 2 with management modification). Three baseline factors were associated with pemetrexed ELT in univariate and multivariate analysis: cystatin clearance (p = 0.0135), albumin level (p = 0.0333), and proton pump inhibitors use (p = 0.035).
CONCLUSION
To conclude, ELT induced by pemetrexed-based treatments occur frequently in cancer patients in a real-world setting. A pretherapeutic assessment before pemetrexed initiation should include three major checkpoints: use of proton pump inhibitors, sarcopenia, and denutrition evaluation.
Topics: Humans; Aged; Pemetrexed; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Retrospective Studies; Proton Pump Inhibitors; Mesothelioma; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36951965
DOI: 10.1007/s00228-023-03478-4 -
Indian Journal of Cancer 2020
Review
Topics: Aged; Aged, 80 and over; Feasibility Studies; Female; Humans; Middle Aged; Ovarian Neoplasms; Pemetrexed; Retrospective Studies; Salvage Therapy
PubMed: 33078762
DOI: 10.4103/ijc.IJC_284_19 -
Clinical Lung Cancer Jan 2018Pemetrexed is a standard first-line treatment for advanced nonsquamous non-small-cell lung cancer (NSCLC), and epidermal growth factor receptor (EGFR) tyrosine kinase... (Review)
Review
A Review of Regimens Combining Pemetrexed With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in the Treatment of Advanced Nonsquamous Non-Small-Cell Lung Cancer.
Pemetrexed is a standard first-line treatment for advanced nonsquamous non-small-cell lung cancer (NSCLC), and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a standard first-line treatment for advanced nonsquamous NSCLC with activating EGFR mutations. Pemetrexed and EGFR TKIs have different mechanisms of action and minimally overlapping toxicity profiles; therefore, it is hypothesized that their combination might result in acceptable toxicity, provided that the synergistic antitumor activity observed in preclinical studies is achieved. This review summarizes clinical trials of pemetrexed in combination with an EGFR TKI for the treatment of advanced nonsquamous NSCLC in the first- and second-line settings, using intercalated, sequential, and concurrent treatment strategies. As would be expected, such strategies were most efficacious in patients with the activating EGFR mutations associated with response to an EGFR TKI. In the studies that compared a pemetrexed-EGFR TKI combination with pemetrexed alone or the EGFR TKI alone, the pemetrexed-EGFR TKI combination was more efficacious than the single-agent regimens. The pemetrexed-EGFR TKI combinations were generally associated with a higher incidence of grade 3/4 treatment-related adverse events than the single-agent regimens; however, such toxicities were clinically manageable. Future studies of pemetrexed-EGFR TKI combinations should focus on optimizing treatment strategies in patients with activating EGFR mutations.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Neoplasm Staging; Pemetrexed; Protein Kinase Inhibitors
PubMed: 28743421
DOI: 10.1016/j.cllc.2017.06.013