Impact of Use of Gastric-Acid Suppressants and Oral Anti-Cancer Agents on Survival Outcomes: A Systematic Review and Meta-Analysis

Indini, Alice; Petrelli, Fausto; Tomasello, Gianluca; Rijavec, Erika; Facciorusso, Antonio; Grossi, Francesco; Ghidini, Michele

doi:10.3390/cancers12040998

Cited by 26 publications

(35 citation statements)

References 43 publications

(58 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…OS (HR =1.46, 95% CI: 1.27-1.67; P<0.00001; Figure 3) and PFS (HR =1.63, 95% CI: 1.35-1.98; P<0.00001; Figure 4) both favored patients treated with EGFR TKI only. Similar to a previous meta-analysis on the impact of concurrent administration of EGFR TKIs and AS on various cancers (33), this meta-analysis found better survival outcomes for OS and PFS when only EGFR-TKIs were used. When combined with AS medications that lower the gastric pH, the alterations in pharmacokinetics of oral EGFR-TKIs led to a decrease in absorption and bioavailability of these drugs, possibly increasing the risk of disease progression and eventually poorer survival.…”

Section: Discussionsupporting

confidence: 79%

“…The findings of this study are limited to NSCLC patients receiving first-generation EGFR TKIs (erlotinib and gefitinib). The clinical effect of AS on afatinib efficacy has not been delineated and past studies have also reported that afatinib remained soluble across a wide pH range of 1-7 (33). Other EGFR TKIs such as second-generation dacomitinib and third generation osimertinib were also not analyzed in this study.…”

Section: Rashmentioning

confidence: 99%

See 1 more Smart Citation

Interactions between epidermal growth factor receptor tyrosine kinase inhibitors and proton-pump inhibitors/histamine type-2 receptor antagonists in non-small cell lung cancer: a systematic review and meta-analysis

Sim¹,

Jain²,

Lim³

et al. 2021

Transl Lung Cancer Res

View full text Add to dashboard Cite

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are increasingly used for advanced non-small cell lung cancer (NSCLC) as first-line therapy. The bioavailability and efficacy of oral EGFR-TKIs could be affected by acid suppression (AS) therapy such as PPIs and H2RAs which are reported to be over-prescribed. Hence, there is a need to investigate the effect of AS on the overall survival (OS), progression-free survival (PFS) and adverse effect profile in patients treated with EGFR TKIs.Methods: An electronic database search of Medline and Embase was performed following PRISMA guidelines on 17 January 2021. Studies analyzing interactions between EGFR TKIs and PPIs/H2RAs in NSCLC patients were included. Abstracts, non-English or non-Japanese studies or studies using non-EGFR TKIs were excluded. Hazard ratios (HRs) were pooled using generic inverse variance random effects model. Effect sizes for dichotomous variables were pooled using Mantel-Haenszel random effects model. Significance was considered at P≤0.05. Heterogeneity was assessed with Cochran Q-test and I2 test.Publication bias was assessed with funnel plots. The assessment of quality and risk of bias of randomized and non-randomized studies were undertaken with RoB 2 and the ROBINS-I tool respectively.Results: Out of 1,173 potentially relevant articles, 14 articles were included in the final analysis. The pooled prevalence of AS in patients taking EGFR TKI was 30.71% in 4,010 individuals. Patients who were treated only with EGFR TKI had significantly better OS (HR =1.46, 95% CI: 1.27-1.72; P<0.00001) and PFS (HR =1.63, 95% CI: 1.35-1.98; P<0.00001). The OS for EGFR mutation positive patients only was as similarly significant as the OS in all patients taking EGFR TKI, while the PFS in mutation positive patients was significantly worsened with AS. PPIs resulted in a significantly worsened OS and PFS but H2RAs did not produce significantly different OS and PFS between AS and non-AS users. There were no significant differences in the incidence of rash (OR =0.81, 95% CI: 0.50-1.32; P=0.40), diarrhoea 3568 Sim et al. Interactions of EGFR TKIs and PPIs/H2RAs in NSCLC

show abstract

Section: Discussionsupporting

confidence: 79%

Section: Rashmentioning

confidence: 99%

Interactions between epidermal growth factor receptor tyrosine kinase inhibitors and proton-pump inhibitors/histamine type-2 receptor antagonists in non-small cell lung cancer: a systematic review and meta-analysis

Sim¹,

Jain²,

Lim³

et al. 2021

Transl Lung Cancer Res

View full text Add to dashboard Cite

show abstract

“…The pH surface value can be calculated using the Mooney-Stella equation [21][22][23][24]. The solid surface solubility (S surface, ST ) can be calculated from pH surface and S 0 , similar to Equation (7). The dissolution rate coefficient in the stomach (k diss, ST ) can be calculated as,…”

Section: Dissolution Rate In the Stomachmentioning

confidence: 99%

“…In the case of poorly soluble weak base drugs, gastric dissolution can have a marked impact on their oral absorption. Drug-drug interactions (DDI) with gastric acid-reducing agents (ARA), such as antacids, H 2 blockers, and proton pump inhibitors, are of great clinical importance, as they could reduce the efficacy of a drug by interfering with gastric dissolution [ 6 , 7 , 8 ]. In addition, elderly subjects tend to be achlorhydric [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Bottom-Up Physiologically Based Oral Absorption Modeling of Free Weak Base Drugs

et al. 2020

View full text Add to dashboard Cite

In this study, we systematically evaluated “bottom-up” physiologically based oral absorption modeling, focusing on free weak base drugs. The gastrointestinal unified theoretical framework (the GUT framework) was employed as a simple and transparent model. The oral absorption of poorly soluble free weak base drugs is affected by gastric pH. Alternation of bulk and solid surface pH by dissolving drug substances was considered in the model. Simple physicochemical properties such as pKa, the intrinsic solubility, and the bile micelle partition coefficient were used as input parameters. The fraction of a dose absorbed (Fa) in vivo was obtained by reanalyzing the pharmacokinetic data in the literature (15 drugs, a total of 85 Fa data). The AUC ratio with/without a gastric acid-reducing agent (AUCr) was collected from the literature (22 data). When gastric dissolution was neglected, Fa was underestimated (absolute average fold error (AAFE) = 1.85, average fold error (AFE) = 0.64). By considering gastric dissolution, predictability was improved (AAFE = 1.40, AFE = 1.04). AUCr was also appropriately predicted (AAFE = 1.54, AFE = 1.04). The Fa values of several drugs were slightly overestimated (less than 1.7-fold), probably due to neglecting particle growth in the small intestine. This modeling strategy will be of great importance for drug discovery and development.

show abstract

“…ADH expression has the potential to be a prognostic marker of pancreatic adenocarcinoma[ 25 ], and acetaldehyde is recognized to elevate the possibility of chemically induced rectal carcinogenesis[ 26 ]. A recent meta-analysis revealed that gastric acid suppressant use showed a significant correlation with poor survival for patients receiving oral chemotherapy for gastrointestinal tract cancer, supporting a possible negative impact of gastric acid suppressants on the survival outcome of CRC[ 27 ]. As one of the most fundamental requirements for biosynthesis, nitrogen metabolism is utilized and modulated to sustain the increased demand for nitrogen sources in cancer proliferation[ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of the circRNA-miRNA-mRNA regulatory network and its prognostic effect in colorectal cancer

Yin¹,

Zhao²,

Zhou³

et al. 2021

WJCC

View full text Add to dashboard Cite

BACKGROUND The high morbidity and mortality of colorectal cancer (CRC) have posed great threats to human health. Circular RNA (CircRNA) and microRNA (miRNA), acting as competing endogenous RNAs (ceRNAs), have been found to play vital roles in carcinogenesis. However, the biological function of ceRNAs in CRC pathogenesis and prognosis remains largely unexplored. AIM To identify the CRC-specific circRNA-miRNA-mRNA regulatory network and uncover the subnetwork associated with its prognosis. METHODS CircRNAs, miRNAs and mRNAs differentially expressed (DE) in CRC tissues were selected by expression file analysis in the Gene Expression Omnibus (GEO) database, and the downstream target molecules of circRNAs and miRNAs were predicted. Then, the intersection of differentially expressed RNA molecules with the predicted targets was determined to obtain a ceRNA network. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to elucidate the possible mechanism of pathogenesis. A survival analysis using the gene profiles and clinical information in The Cancer Genome Atlas (TCGA) database was performed to identify the mRNAs associated with the clinical outcome of CRC patients and construct a prognostic subnetwork. RESULTS We downloaded three datasets (GSE126095, GSE41655 and GSE41657) of large-scale CRC samples from the GEO database. There were 55 DEcircRNAs, 114 DEmiRNAs and 267 DEmRNAs in CRC tissues compared with normal tissues. After intersecting these molecules with predicted targets, 19 circRNAs, 13 miRNAs and 28 mRNAs were chosen to develop a circRNA-miRNA-mRNA network. GO and KEGG functional enrichment analyses indicated that the retinol metabolic process, leukocyte chemotaxis, extracellular matrix remodeling, endoplasmic reticulum stress, alcohol dehydrogenase activity, gastric acid secretion, nitrogen metabolism and NOD-like receptor signaling pathway might participate in the tumorigenesis of CRC. After verifying the identified mRNA effect in the TCGA database, we finally recognized 3 mRNAs ( CA2, ITLN1 and LRRC19 ) that were significantly associated with the overall survival of CRC patients and constructed a ceRNA subnetwork including 5 circRNAs (hsa_circ_0080210, hsa_circ_0007158, hsa_circ_0000375, hsa_circ_0018909 and hsa_circ_0011536) and 3 miRNAs (hsa-miR-601, hsa-miR-671-5p and hsa-miR-765), which could contain innovative and noninvasive indicators for the early screening and prognostic prediction of CRC. CONCLUSION We proposed a circRNA-miRNA-mRNA regulatory network closely associated with the progression and clinical outcome of CRC that might include promising biomarkers for carcinogenesis and therapeutic targets.

show abstract

Impact of Use of Gastric-Acid Suppressants and Oral Anti-Cancer Agents on Survival Outcomes: A Systematic Review and Meta-Analysis

Cited by 26 publications

References 43 publications

Interactions between epidermal growth factor receptor tyrosine kinase inhibitors and proton-pump inhibitors/histamine type-2 receptor antagonists in non-small cell lung cancer: a systematic review and meta-analysis

Interactions between epidermal growth factor receptor tyrosine kinase inhibitors and proton-pump inhibitors/histamine type-2 receptor antagonists in non-small cell lung cancer: a systematic review and meta-analysis

Bottom-Up Physiologically Based Oral Absorption Modeling of Free Weak Base Drugs

Identification of the circRNA-miRNA-mRNA regulatory network and its prognostic effect in colorectal cancer

Contact Info

Product

Resources

About