Serum Concentration of Erlotinib and its Correlation with Outcome and Toxicity in Patients with Advanced-stage NSCLC

Fiala, Ondřej; Hošek, Petr; Pešek, Miloš; Fínek, Jindřich; Ráček, Jaroslav; Stehlík, Pavel; Šorejs, Ondřej; Minárik, Marek; Benešová, Lucie; Celer, Adam; I, Nemcová; Kučera, Radek; Topolčan, Ondřej

doi:10.21873/anticanres.12102

Cited by 8 publications

(6 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…9,19 Numerous studies have reported targets or promising candidate C min,ss values for EGFR-TKI and ALK inhibitors (Table 1). [7][8][9][10][11][12][13][14][15][16][17][18][19]21,22 To the best of our knowledge, the present method can be used to determine the concentrations of a greater number of EGFR-TKIs and ALK inhibitors than any other known analytical method for the simultaneous quantification of various TKIs. [23][24][25][26][27][28][29][30][31][32][33][34] The run time of this method is 7 minutes, which is shorter than the run time of a published conventional LC-MS/MS-based method.…”

Section: Discussionmentioning

confidence: 99%

“…9,19 Numerous studies have reported targets or promising candidate C min,ss values for EGFR-TKI and ALK inhibitors (Table 1). 7–19,21,22…”

Section: Discussionmentioning

confidence: 99%

“…2,3 Currently, EGFR-tyrosine kinase inhibitors (TKIs) and ALK inhibitors are used in the treatment of NSCLC. [4][5][6] Several studies have revealed relationships between the exposure efficacy and exposure safety of afatinib, 7,8 alectinib, 9 ceritinib, 10 crizotinib, 9,11 dacomitinib, 12 erlotinib, [13][14][15] gefitinib, 16,17 and osimertinib. 18 However, the achievement of target concentrations fails to occur in 11%-48% of patients taking standard doses of alectinib, crizotinib, erlotinib, or gefitinib.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

An Liquid Chromatography–Tandem Mass Spectrometry Method for the Simultaneous Determination of Afatinib, Alectinib, Ceritinib, Crizotinib, Dacomitinib, Erlotinib, Gefitinib, and Osimertinib in Human Serum

Mukai

Wakamoto

Hatsuyama

et al. 2021

Therapeutic Drug Monitoring

View full text Add to dashboard Cite

Background: Routine therapeutic drug monitoring is a promising approach for the rational use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and anaplastic lymphoma kinase (ALK) inhibitors. The purpose of this study was to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of 5 EGFR-TKIs (afatinib, dacomitinib, erlotinib, gefitinib, and osimertinib) and 3 ALK inhibitors (alectinib, ceritinib, and crizotinib).Methods: A 100-mL aliquot of serum was diluted with 100 mL of 1% aqueous ammonia containing internal standards and then purified using the supported liquid extraction method. LC-MS/MS was conducted in positive ionization mode, and the method was validated according to published guidelines.Results: Calibration curves were linear across concentration ranges examined. The intra-and interassay accuracies were 90.7%-110.7% and 94.7%-107.6%, respectively. All intra-and interassay imprecision values were #10.1%. The EGFR-TKIs and ALK inhibitors examined in this study, except osimertinib, which could be stored on ice for at least 5 hours, were stable at room temperature for 3 hours. For the internal standard-normalized matrix factors, the mean recovery and percent coefficient of variation values ranged between 54%-112% and 1.7%-11.7%, respectively. This method successfully determined serum concentrations of afatinib, alectinib, erlotinib, gefitinib, and osimertinib in clinical samples. Serum levels of kinase inhibitors consistently reflected those reported in previous studies.Conclusions: An LC-MS/MS method suitable for the simultaneous determination of 5 EGFR-TKIs and 3 ALK inhibitors in serum was developed and validated. The newly developed method enabled the determination of 5 of 8 target drugs examined in clinical samples. However, a large number of clinical samples need to be analyzed to verify the usefulness of the method.

show abstract

Section: Discussionmentioning

confidence: 99%

“…9,19 Numerous studies have reported targets or promising candidate C min,ss values for EGFR-TKI and ALK inhibitors (Table 1). 7–19,21,22…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An Liquid Chromatography–Tandem Mass Spectrometry Method for the Simultaneous Determination of Afatinib, Alectinib, Ceritinib, Crizotinib, Dacomitinib, Erlotinib, Gefitinib, and Osimertinib in Human Serum

Mukai

Wakamoto

Hatsuyama

et al. 2021

Therapeutic Drug Monitoring

View full text Add to dashboard Cite

show abstract

“…However, solid evidence in humans (with the equivalent doses) is missing. At the approved dose, associations between systemic drug exposure and the development of rash and diarrhea have been reported [22,34]. The development of these adverse events was observed to be far less for erlotinib 25-100 mg QD or gefitinib 250 mg on alternating days [24][25][26][27][28][29]35].…”

Section: First-generation Egfr Smismentioning

confidence: 99%

Optimized Dosing: The Next Step in Precision Medicine in Non-Small-Cell Lung Cancer

Boosman

Burgers

Smit

et al. 2021

Drugs

View full text Add to dashboard Cite

In oncology, and especially in the treatment of non-small-cell lung cancer (NSCLC), dose optimization is often a neglected part of precision medicine. Many drugs are still being administered in "one dose fits all" regimens or based on parameters that are often only minor determinants for systemic exposure. These dosing approaches often introduce additional pharmacokinetic variability and do not add to treatment outcomes. Fortunately, pharmacological knowledge is increasing, providing valuable information regarding the potential of, for example, therapeutic drug monitoring. This article focuses on the evidence for the most promising and easily implemented optimized dosing approaches for the small-molecule inhibitors, chemotherapeutic agents, and monoclonal antibodies as treatment options currently approved for NSCLC. Despite limitations such as investigations having been conducted in oncological diseases other than NSCLC or the retrospective origin of many analyses, an alternative dosing regimen could be beneficial for treatment outcomes, prescriber convenience, or financial burden on healthcare systems. This review of the literature provides recommendations on the implementation of dose optimization and advice regarding promising strategies that deserve further research in NSCLC.

show abstract

“…For erlotinib, two studies on an E-R relationship have recently been published and these could not identify a relationship between exposure and PFS or OS (resp. in 70 and 122 NSCLC patients) [ 70 , 71 ]. It has been suggested that reduced doses (e.g., 100 or 50 mg/day for erlotinib) could reduce toxicity while maintaining efficacy, especially in frail patients [ 72 , 73 ].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

van der Kleij,

Guchelaar,

Mathijssen

et al. 2023

Clin Pharmacokinet

View full text Add to dashboard Cite

Although kinase inhibitors (KI) frequently portray large interpatient variability, a ‘one size fits all’ regimen is still often used. In the meantime, relationships between exposure-response and exposure-toxicity have been established for several KIs, so this regimen could lead to unnecessary toxicity and suboptimal efficacy. Dose adjustments based on measured systemic pharmacokinetic levels—i.e., therapeutic drug monitoring (TDM)—could therefore improve treatment efficacy and reduce the incidence of toxicities. Therefore, the aim of this comprehensive review is to give an overview of the available evidence for TDM for the 77 FDA/EMA kinase inhibitors currently approved (as of July 1st, 2023) used in hematology and oncology. We elaborate on exposure-response and exposure-toxicity relationships for these kinase inhibitors and provide practical recommendations for TDM and discuss corresponding pharmacokinetic targets when possible.

show abstract

Serum Concentration of Erlotinib and its Correlation with Outcome and Toxicity in Patients with Advanced-stage NSCLC

Abstract: Erlotinib concentration was not associated with outcome. Erlotinib concentration was associated with occurrence and severity of skin rash and diarrhoea; the outcome was associated with erlotinib toxicity.

Cited by 8 publications

References 20 publications

An Liquid Chromatography–Tandem Mass Spectrometry Method for the Simultaneous Determination of Afatinib, Alectinib, Ceritinib, Crizotinib, Dacomitinib, Erlotinib, Gefitinib, and Osimertinib in Human Serum

An Liquid Chromatography–Tandem Mass Spectrometry Method for the Simultaneous Determination of Afatinib, Alectinib, Ceritinib, Crizotinib, Dacomitinib, Erlotinib, Gefitinib, and Osimertinib in Human Serum

Optimized Dosing: The Next Step in Precision Medicine in Non-Small-Cell Lung Cancer

Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

Contact Info

Product

Resources

About