Risk of selected gastrointestinal toxicities in patients with advanced non-small cell lung cancer receiving erlotinib: a systematic review and meta-analysis

Abdel‐Rahman, Omar; Fouad, Mona

doi:10.1586/14737140.2015.1014035

Cited by 13 publications

(3 citation statements)

References 28 publications

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“…Most of the meta-analyses focused on the effect of EGFR-TKIs 4 , 29 – 31 have been published; some studies that determined the toxicity mostly focused on the fatal AEs such as treatment-related mortality, 32 interstitial lung disease, 9 skin rash, 33 and gastrointestinal toxicities. 34 To the best of our knowledge, this is the first meta-analysis to demonstrate a significantly decreased risk of ≥grade 3 neutropenia and leukopenia as a result of erlotinb-related treatment compared with CT. Many RCTs focused on the effect of erlotinib in advanced NSCLC, 5 – 7 , 21 - 28 the effect including PFS, OS, objective response rate, and so on.…”

Section: Discussionmentioning

confidence: 77%

The Risk of Neutropenia and Leukopenia in Advanced Non-Small Cell Lung Cancer Patients Treated With Erlotinib

Zhou

Tian

Cheng³

et al. 2015

Medicine

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Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a critical member of systemic therapy for advanced non-small-cell lung cancer (NSCLC). Erlotinib is the first-generation EGFR-TKIs, the National Comprehensive Cancer Network (NCCN) guidelines recommend it as a first-line agent in patients with sensitizing EGFR mutations. However, the safety of erlotinib plus chemotherapy (CT) or erlotinib alone for advanced NSCLC remains controversial. We carried out a systematic meta-analysis to determine the overall risk of neutropenia and leukopenia associated with erlotinib.PubMed, EMBASE, CBM, CNKI, WanFang database, The Cochrane library, Web of Science, as well as abstracts presented at ASCO conferences and ClinicalTrials.gov were searched to identify relevant studies. RR with 95% CIs for neutropenia and leukopenia were all extracted. The random-effects model was used to calculate pooled RRs and 95% CIs. Power calculation was performed using macro embedded in SAS software after all syntheses were conducted.We identified 12 eligible studies involving 3932 patients. Erlotinib plus CT or alone relative to CT is associated with significantly decreased risks of neutropenia and leukopenia in patients with advanced NSCLC (RR, 0.38; 95% CI, 0.21–0.71; P = 0.00; incidence: 9.9 vs. 35.2%) and (RR, 0.32; 95% CI, 0.11–0.93; P = 0.04; incidence: 3.5 vs. 11.6%), respectively. The subgroup analysis by erlotinb with or without CT showed that erlotinib combine with CT have no significance decrease the relative risks of neutropenia or leukopenia (RR, 0.98; 95% CI, 0.78–1.23; P = 0.87; incidence: 26.2 vs. 30.5%) and (RR, 0.81; 95% CI, 0.34–1.95; P = 0.64; incidence: 6.5 vs. 9.3%), respectively. However, erlotinib alone could decrease incidence of neutropenia (RR, 0.14; 95% CI, 0.07–0.27; P = 0.00; incidence: 3.7 vs. 40.8%) or leukopenia (RR, 0.07; 95% CI, 0.01–0.45; P = 0.01; incidence: 0.8 vs. 15.7%). The power analysis suggests that a power of 61.31% was determined to detect an RR of 0.38 for neutropenia, and 78.03% for an RR of 0.32 for leukopenia.The present meta-analysis suggested that erlotinib could decrease the incidence of neutropenia and leukopenia in patients with advanced NSCLC undergoing erlotinib regardless of whether combined with CT or not. The subgroup analysis revealed that erlotinib combine with CT did not affect the incidence; however, erlotinib alone could significantly decrease the incidence of neutropenia and leukopenia compared with CT alone.

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Section: Discussionmentioning

confidence: 77%

The Risk of Neutropenia and Leukopenia in Advanced Non-Small Cell Lung Cancer Patients Treated With Erlotinib

Zhou

Tian

Cheng³

et al. 2015

Medicine

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“…GI toxicities have long been reported also in a number of other targeted therapeutics used in cancer management and, likewise, they have been linked to dose reduction and/or interruption [32,33].…”

Section: Discussionmentioning

confidence: 99%

Risk of selected gastrointestinal toxicities in cancer patients treated with MEK inhibitors: a comparative systematic review and meta-analysis

Abdel‐Rahman

Elhalawani

Ahmed

et al. 2015

Expert Review of Gastroenterology & Hepatology

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We performed a systematic review and meta-analysis of the risk of gastrointestinal (GI) toxicities associated with MEK inhibitors. Eligible studies included randomized Phase II and III trials of cancer patients on the three MEK inhibitors (trametinib, selumetinib and cobimetinib), describing events of stomatitis, diarrhea and vomiting. Our search strategy yielded 250 potentially relevant citations from Pubmed/Medline, Google scholar and CENTRAL Cochrane registry. After exclusion of ineligible studies, a total of 16 clinical trials were considered eligible for the meta-analysis. The relative risks of all-grade stomatitis, diarrhea and vomiting were 2.03 (95% CI 1.41-2.96; p = 0.002), 1.92 (95% CI 1.48-2.50; p < 0.00001) and 1.35 (95% CI 1.06-1.71; p = 0.01). Subgroup analyses according to agent used (trametinib vs Selumetinib), the regimen used (monotherapy vs combination) and the cancer treated (melanoma vs nonmelanoma) did not reveal any significant difference between the subgroups. Our meta-analysis has demonstrated that MEK inhibitor-based treatment is associated with an increased risk of stomatitis, diarrhea and vomiting compared to control. Clinicians should be aware of this risk and perform regular assessment.

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“…Gastrointestinal disorders are very common adverse events of cancer treatments including chemotherapy and targeted therapies. Erlotinib induces diarrhoea in 10·2% to 67% of patients with NSCLC, whereas rates of high‐grade diarrhoea range from 0·6% to 12·5% . A meta‐analysis found that the addition of an EGFR‐TKI to a chemotherapy significantly increased the incidence of diarrhoea .…”

Section: Details Of the Casementioning

confidence: 99%

Chemotherapy (platinum and pemetrexed) in combination with erlotinib in non-small cell lung cancer induces major gastrointestinal toxicity: two case reports from the FLARE/GFPC 03-2013 study

et al. 2016

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Risk of selected gastrointestinal toxicities in patients with advanced non-small cell lung cancer receiving erlotinib: a systematic review and meta-analysis

Cited by 13 publications

References 28 publications

The Risk of Neutropenia and Leukopenia in Advanced Non-Small Cell Lung Cancer Patients Treated With Erlotinib

The Risk of Neutropenia and Leukopenia in Advanced Non-Small Cell Lung Cancer Patients Treated With Erlotinib

Risk of selected gastrointestinal toxicities in cancer patients treated with MEK inhibitors: a comparative systematic review and meta-analysis

Chemotherapy (platinum and pemetrexed) in combination with erlotinib in non-small cell lung cancer induces major gastrointestinal toxicity: two case reports from the FLARE/GFPC 03-2013 study

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