Clinical pharmacokinetics of erlotinib in patients with solid tumors and exposure-safety relationship in patients with non–small cell lung cancer

Lu, Jianfeng; Eppler, Steve; Wolf, Julie; Hamilton, Marta; Rakhit, Ashok; Bruno, René; Lum, Bert L.

doi:10.1016/j.clpt.2006.04.007

Cited by 200 publications

(169 citation statements)

References 24 publications

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“…However, there was significant overlap in the range of PK values with patients who had no rash. No correlation was found with diarrhea 31. Two clinical exposure–response studies have been reported.…”

Section: Practical Recommendations For Tdm Of Kis In Oncologymentioning

confidence: 98%

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Practical Recommendations for Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

Verheijen

Schellens

et al. 2017

Clin Pharma and Therapeutics

228

287

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Despite the fact that pharmacokinetic exposure of kinase inhibitors (KIs) is highly variable and clear relationships exist between exposure and treatment outcomes, fixed dosing is still standard practice. This review aims to summarize the available clinical pharmacokinetic and pharmacodynamic data into practical guidelines for individualized dosing of KIs through therapeutic drug monitoring (TDM). Additionally, we provide an overview of prospective TDM trials and discuss the future steps needed for further implementation of TDM of KIs.

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Section: Practical Recommendations For Tdm Of Kis In Oncologymentioning

confidence: 98%

“…Erlotinib exposure has been significantly correlated with rash in several studies 31. However, there was significant overlap in the range of PK values with patients who had no rash.…”

Section: Practical Recommendations For Tdm Of Kis In Oncologymentioning

confidence: 99%

Practical Recommendations for Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

Verheijen

Schellens

et al. 2017

Clin Pharma and Therapeutics

228

287

View full text Add to dashboard Cite

show abstract

“…This deficit can partly be attributed to the traditional nature of cancer drugs, being highly toxic and the use of maximum tolerated doses, making the use of a therapeutic PD endpoint of limited value. Although this latter point may be disputed, it is clear that the majority of PD modeling efforts for anticancer drugs have been models for drug-induced myelosuppression, a common dose-limiting toxicity (42)(43)(44)(45). With the advent of imatinib at the turn of the century, the gateway for targeted anticancer therapy was opened that escalated the opportunities and altered the landscape for multidrug combination cancer chemotherapy as less toxic targeted drugs could be considered (46).…”

Section: Hybrid Physiologically Based Pharmacokinetic/pharmacodynamicmentioning

confidence: 99%

The Pharmacokinetic/Pharmacodynamic Pipeline: Translating Anticancer Drug Pharmacology to the Clinic

Zhou

Gallo

2011

AAPS J

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Abstract. Progress in an understanding of the genetic basis of cancer coupled to molecular pharmacology of potential new anticancer drugs calls for new approaches that are able to address key issues in the drug development process, including pharmacokinetic (PK) and pharmacodynamic (PD) relationships. The incorporation of predictive preclinical PK/PD models into rationally designed early-stage clinical trials offers a promising way to relieve a significant bottleneck in the drug discovery pipeline. The aim of the current review is to discuss some considerations for how quantitative PK and PD analyses for anticancer drugs may be conducted and integrated into a global translational effort, and the importance of examining drug disposition and dynamics in target tissues to support the development of preclinical PK/ PD models that can be subsequently extrapolated to predict pharmacologic characteristics in patients. In this article, we describe three different physiologically based (PB) PK modeling approaches, i.e., the whole-body PBPK model, the hybrid PBPK model, and the two-pore model for macromolecules, as well as their applications. General conclusions are that greater effort should be made to generate more clinical data that could validate scaled preclinical PB-PK/PD tumor-based models and, thus, stimulate a framework for preclinical to clinical translation. Finally, given the innovative techniques to measure tissue drug concentrations and associated biomarkers of drug responses, development of predictive PK/ PD models will become a standard approach for drug discovery and development.KEY WORDS: anticancer drugs; drug discovery and development; pharmacokinetic/pharmacodynamic model; physiologically based pharmacokinetic model.

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“…Upon absorption, erlotinib is heavily protein-bound (93-95 %) to albumin and α-1 acid glycoprotein, and its median half-life is 36 hours [37]. There is no significant association with drug clearance and gender, weight, or age [33].…”

Section: Pharmacologymentioning

confidence: 93%

Tyrosine kinase inhibitors for EGFR- and ALK-mutated non-small cell lung cancer

Thompson

Menon

2016

ADMET DMPK

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Discovery of the epidermal growth receptor (EGFR) activating mutations and anaplastic lymphoma kinase (ALK) rearrangements has expanded the therapeutic landscape in non-small cell lung cancer (NSCLC). Survival outcomes for patients with these mutations have improved dramatically with EGFR and ALK tyrosine kinase inhibitors (TKIs). Multiple generations of EGFR and ALK TKIs have been rapidly developed, and patients and clinicians now have several options for first-and second-line treatments. While these small molecule

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Clinical pharmacokinetics of erlotinib in patients with solid tumors and exposure-safety relationship in patients with non–small cell lung cancer

Abstract: The long half-life of erlotinib supports the current once-daily dosing regimen at 150 mg/d. Effects of covariates on erlotinib clearance and correlations with adverse event severity were provided to aid in the detection of a treatment-emergent effect.

Cited by 200 publications

References 24 publications

Practical Recommendations for Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

Practical Recommendations for Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology

The Pharmacokinetic/Pharmacodynamic Pipeline: Translating Anticancer Drug Pharmacology to the Clinic

Tyrosine kinase inhibitors for EGFR- and ALK-mutated non-small cell lung cancer

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