Pharmacokinetic and Pharmacogenetic Study of Etoposide in High-Dose Protocol (TI-CE) for Advanced Germ Cell Tumors.

Pharmaceutical Research
Sotheara MoeungFabienne Thomas

Abstract

Etoposide dosing is based on body surface area. We evaluated if further dose individualization would be required for high dose (HD) etoposide within the TI-CE (taxol, ifosfamide, carboplatin, and etoposide) protocol. Eighty-eight patients received 400 mg/m2/day of etoposide as a 1-hour IV infusion on 3 consecutive days over 3 cycles as part of a phase II trial evaluating efficacy of therapeutic drug monitoring (TDM) of carboplatin in the TI-CE HD protocol. Pharmacokinetic (PK) data were analyzed using population PK model on NONMEM to quantify inter- and intra-individual variabilities. Relationship between etoposide exposure and pharmacodynamic (PD) endpoints, and between selected genetic polymorphisms and tumor response or toxicity were evaluated. The inter-patient, inter- and intra-cycle variabilities of clearance were 16%, 9% and 0.1%, respectively. The PK-PD relationship was not significant despite a trend toward higher etoposide exposure in patients responding to treatment. A significant correlation was found between exposure and extended neutropenia at cycle 3. A significant association between UGT1A1*28 polymorphism and late neutropenia was observed but needs further evaluation. The present study suggests that neither a p...Continue Reading

References

Oct 1, 1991·Clinical Pharmacology and Therapeutics·C F StewartW E Evans
Jan 1, 1991·Cancer·R H Herzig
Aug 1, 1991·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M J RatainF Berezin
Nov 1, 1990·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·C F StewartW E Evans
Nov 1, 1986·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·S G ArbuckW E Evans
Jan 1, 1995·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·H MinamiK Shimokata
Dec 1, 1994·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·S J HorningK G Blume
Jan 1, 1996·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·S P JoelM L Slevin
Jan 27, 1998·Cancer Chemotherapy and Pharmacology·L NguyenP Canal
Mar 11, 1999·Cancer Chemotherapy and Pharmacology·B TranchandC J Ardiet
Mar 15, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·R J MotzerG J Bosl
Dec 12, 2001·British Journal of Clinical Pharmacology·G ToffoliM Boiocchi
Nov 27, 2002·Therapeutic Drug Monitoring·Joseph CiccoliniAlain Durand
Jun 1, 2010·Human Genomics·Sara Correia Marques, Ogechi N Ikediobi
Sep 21, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sotheara MoeungFabienne Thomas

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
genotyping

Clinical Trials Mentioned

NCT00864318

Software Mentioned

NONMEM
Visual Predictive Check ( VPC )
STATA
SNPassoc
R

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

The New England Journal of Medicine
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
S Z FieldsR H Barbhaiya
Clinical Pharmacy
N C Phillips, R D Lauper
Clinical Pharmacy
R A FlemingC F Stewart
© 2021 Meta ULC. All rights reserved