Influence of the Acidic Beverage Cola on the Absorption of Erlotinib in Patients With Non–Small-Cell Lung Cancer

Leeuwen, Roelof W F van; Peric, Robert; Hussaarts, Koen G A M; Kienhuis, Emma; IJzerman, Nikki S.; Bruijn, Peter de; Leest, Cor van der; Codrington, Henk; Kloover, Jeroen S.; Aerts, Joachim; Gelder, Teun van; Mathijssen, Ron H.J.

doi:10.1200/jco.2015.65.2560

Cited by 104 publications

(80 citation statements)

References 14 publications

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“…It was therefore investigated whether co‐administration of imatinib with an acidic beverage could increase the exposure to imatinib. This was previously described for erlotinib, but could not be substantiated for imatinib …”

Section: Methodsmentioning

confidence: 99%

Imatinib, sunitinib and pazopanib: From flat‐fixed dosing towards a pharmacokinetically guided personalized dose

Westerdijk¹,

Desar²,

Steeghs

et al. 2020

Brit J Clinical Pharma

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Tyrosine kinase inhibitors (TKIs) are anti‐cancer drugs that target tyrosine kinases, enzymes that are involved in multiple cellular processes. Currently, multiple oral TKIs have been introduced in the treatment of solid tumours, all administered in a fixed dose, although large interpatient pharmacokinetic (PK) variability is described. For imatinib, sunitinib and pazopanib exposure‐treatment outcome (efficacy and toxicity) relationships have been established and therapeutic windows have been defined, therefore dose optimization based on the measured blood concentration, called therapeutic drug monitoring (TDM), can be valuable in increasing efficacy and reducing the toxicity of these drugs. In this review, an overview of the current knowledge on TDM guided individualized dosing of imatinib, sunitinib and pazopanib for the treatment of solid tumours is presented. We summarize preclinical and clinical data that have defined thresholds for efficacy and toxicity. Furthermore, PK models and factors that influence the PK of these drugs which partly explain the interpatient PK variability are summarized. Finally, pharmacological interventions that have been performed to optimize plasma concentrations are described. Based on current literature, we advise which methods should be used to optimize exposure to imatinib, sunitinib and pazopanib.

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Section: Methodsmentioning

confidence: 99%

Imatinib, sunitinib and pazopanib: From flat‐fixed dosing towards a pharmacokinetically guided personalized dose

Westerdijk¹,

Desar²,

Steeghs

et al. 2020

Brit J Clinical Pharma

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show abstract

“…Erlotinib, a small molecule TKI used for non‐small cell lung cancer (NSCLC) and pancreatic cancer, also requires an acidic environment for absorption . Erlotinib concentrations were not found to be reduced in a study investigating erlotinib in combination with intravenous and oral pantoprazole; however, bioavailability was reduced when cola and esomeprazole were administered concomitantly with erlotinib . Furthermore, a study evaluating the effect of concomitant PPI or H2RA with erlotinib showed no significant effect on PFS or OS in patients with NSCLC .…”

Section: Introductionmentioning

confidence: 99%

Effect of Concomitant pH-Elevating Medications with Pazopanib on Progression-Free Survival and Overall Survival in Patients with Metastatic Renal Cell Carcinoma

et al. 2018

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Pazopanib is a preferred category-one first-line treatment for predominant clear cell metastatic renal cell carcinoma (mRCC). However, because of an aging demographic, coupled with patients with mRCC presenting with multiple comorbidities, including symptomatic dyspepsia or gastroesophageal reflux disease, patients are commonly required to take pazopanib concomitantly with a proton pump inhibitor (PPI) or a histamine 2 receptor antagonist (H2RA). Despite earlier pharmacokinetic reports suggesting that an alkaline pH may result in poorer absorption, this institutional retrospective study found no effect on clinical outcomes. These data suggest that concurrent treatment of mRCC with pazopanib and a PPI or H2RA may be safe in everyday practice.

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“…It is just as important to seek out potential pharmacological strategies to eliminate this pharmacokinetic interaction. For instance, van Leeuwen and colleagues recently reported that simply ingesting the acidic beverage Cola with erlotinib improves its bioavailability in patients who are also receiving esomeprazole [31]. Moreover, this study highlights the importance of dietary factors – which are hard to control – in influencing the absorption of oncological TKIs.…”

Section: Discussionmentioning

confidence: 83%

EGFR kinase inhibitors and gastric acid suppressants in EGFR-mutant NSCLC: a retrospective database analysis of potential drug interaction

et al. 2016

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BackgroundErlotinib and gefitinib are weak base drugs whose absorption and clinical efficacy may be impaired by concomitant gastric acid suppressive (AS) therapy, yet proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2As) are widely indicated in non-small cell lung cancer (NSCLC) patients for the prevention and treatment of erlotinib-induced gastrointestinal injury and corticosteroid-associated gastric irritation. We assessed the clinical relevance of this potential drug-drug interaction (DDI) in a retrospective cohort of EGFR-mutant NSCLC patients.ResultsThe AS usage rate was 35%. In the overall cohort, AS users did not experience poorer OS (HR: 1.47, 95% CI: 0.92 – 2.35, P = 0.10; median, 11.4 versus 17.5 months) or PFS (HR = 1.37, 95% CI: 0.89 – 2.12, P = 0.16; median, 7.6 versus 8.7 months) compared with non-users in multivariate Cox regression analysis. However, subgroup analyses indicated that AS usage was associated with significantly poorer OS and PFS in patients who had fewer or milder comorbidities (Charlson comorbidity index ≤ 2), those with Karnofsky performance status < 90, and never-smokers.Materials and MethodsA retrospective database analysis of 157 patients given erlotinib or gefitinib for EGFR-mutant advanced NSCLC from two institutions was conducted. Patients were classified as AS-users if the periods of AS and anti-EGFR therapy overlapped by ≥ 30%. Overall survival (OS) and progression-free survival (PFS) were assessed according to AS usage.ConclusionsConcomitant AS therapy did not have an adverse impact on OS and/or PFS in the overall cohort. Our subgroup findings should be regarded exploratory and require replication in a large prospective cohort.

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Influence of the Acidic Beverage Cola on the Absorption of Erlotinib in Patients With Non–Small-Cell Lung Cancer

Cited by 104 publications

References 14 publications

Imatinib, sunitinib and pazopanib: From flat‐fixed dosing towards a pharmacokinetically guided personalized dose

Imatinib, sunitinib and pazopanib: From flat‐fixed dosing towards a pharmacokinetically guided personalized dose

Effect of Concomitant pH-Elevating Medications with Pazopanib on Progression-Free Survival and Overall Survival in Patients with Metastatic Renal Cell Carcinoma

EGFR kinase inhibitors and gastric acid suppressants in EGFR-mutant NSCLC: a retrospective database analysis of potential drug interaction

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