Meta-analysis examining impact of age on overall survival with pemetrexed for the treatment of advanced non-squamous non-small cell lung cancer

Paz‐Ares, Luis; Zimmermann, Annamaria H.; Ciuleanu, Tudor-Eliade; Bunn, Paul A.; Antonio, Belén San; Denne, Jonathan; Iturria, Nancy; John, William J.; Scagliotti, Giorgio Vittorio

doi:10.1016/j.lungcan.2016.12.007

Cited by 6 publications

(3 citation statements)

References 29 publications

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“…In addition, it has been confirmed as having a slightly different spectrum from other agents used to treat non‐squamous and anaplastic lymphoma kinase‐positive NSCLC . A meta‐analysis of 2671 patients with NSqNSCLC and good PS revealed that the effect of pemetrexed on overall survival did not differ between younger and older patients when cut‐off ages of 65 or 70 years were used . Moreover, in elderly patients aged ≥ 75, pemetrexed was reported to be safe and effective .…”

Section: Discussionmentioning

confidence: 99%

“…11,16 A meta-analysis of 2671 patients with NSqNSCLC and good PS revealed that the effect of pemetrexed on overall survival did not differ between younger and older patients when cut-off ages of 65 or 70 years were used. 17 Moreover, in elderly patients aged ≥ 75, pemetrexed was reported to be safe and effective. 10 Pemetrexed is very effective and causes little toxicity in patients with NSqNSCLC, even in elderly populations.…”

Section: Discussionmentioning

confidence: 99%

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Phase I study of pemetrexed and concurrent radiotherapy for previously untreated elderly patients with locally advanced non‐squamous non‐small cell lung cancer

et al. 2017

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BackgroundChemoradiotherapy is the standard treatment for locally advanced non‐small cell lung cancer (NSCLC); however, it is disputed whether this treatment is suitable for patients aged ≥75. This study was conducted to determine the maximum tolerated dose (MTD) of pemetrexed for use in concurrent radiotherapy for elderly patients with locally advanced non‐squamous NSCLC.MethodsThe eligibility criteria were as follows: aged ≥75 with inoperable stage IIIA or IIIB non‐squamous NSCLC, no history of chemotherapy or radiotherapy, a performance status of 0 or 1, and adequate organ function. The patients were scheduled to receive pemetrexed on days 1, 22, 43, and 64 with concurrent once daily thoracic radiotherapy (60 Gy). The initial pemetrexed dose was 400 (level 1), and it was planned to increase the dose to 500 mg/m2 (level 2).ResultsTwo patients were enrolled in this trial. In the first case, the patient suffered prolonged leukocytopenia, and treatment was discontinued on day 35. In the second case, febrile neutropenia occurred on day 32, and the patient developed drug‐induced pneumonitis and acute respiratory distress syndrome. Both patients experienced dose‐limiting toxicities; therefore, the level 1 dose was considered to be the MTD.ConclusionsDuring combined treatment with pemetrexed and concurrent radiotherapy, a pemetrexed dose of 400 mg/m2 was the MTD; we did not set up a phase II study. Concurrent chemoradiotherapy might be too toxic for elderly patients aged ≥75 with locally advanced NSCLC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Phase I study of pemetrexed and concurrent radiotherapy for previously untreated elderly patients with locally advanced non‐squamous non‐small cell lung cancer

et al. 2017

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“…Pemetrexed, as an inhibitor of thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), arrests tumor cells primarily in the S phase and induces apoptosis in a broad spectrum of solid tumors, including NSCLC . Pemetrexed is widely used for the treatment of non‐squamous NSCLC patients, with a definite curative effect and less toxicity . A preclinical study showed that cytotoxic synergism was observed when TKI‐sensitive human NSCLC cell lines were exposed to concurrent pemetrexed and erlotinib or sequential pemetrexed followed by erlotinib .…”

Section: Introductionmentioning

confidence: 99%

Efficacy of combined icotinib and pemetrexed in EGFR mutant lung adenocarcinoma cell line xenografts

Cui

Zhang

et al. 2018

Thoracic Cancer

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BackgroundThe combination of EGFR tyrosine kinase inhibitors (TKIs) and chemotherapy is thought to increase treatment efficacy in non‐small‐cell lung cancer (NSCLC). This study investigated the efficacy and potential mechanisms of different combined modes of icotinib plus pemetrexed in EGFR‐mutant lung adenocarcinoma cell line xenograft models.MethodsNude mice were subcutaneously injected with EGFR‐mutant human lung adenocarcinoma cells (HCC827) and randomized into six treatment groups. Tumor xenograft volumes were monitored and recorded. Microvessel density (MVD) and proliferation and apoptosis rates were evaluated with CD34 positive cell counting, and Ki‐67 and caspase‐3 scores, respectively, and determined via immunohistochemistry. Thymidylate synthase (TS), EGFR, and downstream signaling molecule expression was detected by Western blotting.ResultsThe volume and weight of tumor xenografts in the sequential pemetrexed followed by icotinib (Pem‐Ico) group and the concurrent icotinib and pemetrexed (Ico + Pem) group were significantly smaller than those in the control, pemetrexed (Pem), icotinib (Ico), and sequential icotinib followed by pemetrexed (Ico‐Pem) groups. Compared to other groups, a decrease in the MVD and proliferation rate and an increase in the apoptosis rate were observed in the Pem‐Ico and Ico + Pem groups. TS expression and EGFR, AKT, and MAPK phosphorylation were significantly reduced in the Pem‐Ico or Ico + Pem groups.ConclusionsPem‐Ico had additive antitumor activity in vivo, similar to Ico + Pem, both of which are suggested as potentially optimized strategies for treating EGFR‐mutant lung adenocarcinoma.

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Treatment Satisfaction of Patients With Advanced Non–Small-cell Lung Cancer Receiving Platinum-based Chemotherapy: Results From a Prospective Cohort Study (PERSONAL)

Visser¹,

Mol

Cheung

et al. 2018

Clinical Lung Cancer

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Meta-analysis examining impact of age on overall survival with pemetrexed for the treatment of advanced non-squamous non-small cell lung cancer

Cited by 6 publications

References 29 publications

Phase I study of pemetrexed and concurrent radiotherapy for previously untreated elderly patients with locally advanced non‐squamous non‐small cell lung cancer

Phase I study of pemetrexed and concurrent radiotherapy for previously untreated elderly patients with locally advanced non‐squamous non‐small cell lung cancer

Efficacy of combined icotinib and pemetrexed in EGFR mutant lung adenocarcinoma cell line xenografts

Treatment Satisfaction of Patients With Advanced Non–Small-cell Lung Cancer Receiving Platinum-based Chemotherapy: Results From a Prospective Cohort Study (PERSONAL)

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