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Population pharmacokinetics of FOLFIRINOX: a review of studies and parameters
- Source :
- Cancer Chemotherapy and Pharmacology, Cancer Chemotherapy and Pharmacology, Springer Verlag, 2019, 83 (1), pp.27-42. ⟨10.1007/s00280-018-3722-5⟩, Cancer Chemotherapy and Pharmacology, 2019, 83 (1), pp.27-42. ⟨10.1007/s00280-018-3722-5⟩
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- FOLFIRINOX regimen is commonly used in colorectal and more recently pancreatic cancer. However, FOLFIRINOX induces significant and dose-limiting toxic effects leading to empirical dose reduction and sometimes treatment discontinuation. Model-based FOLFIRINOX regimen optimization might help improving patients’ outcome. As a first step, the current review aims at bringing together all published population pharmacokinetics models for FOLFIRINOX anticancer drugs. A literature search was conducted in the PubMed database from inception to February 2018, using the following terms: population pharmacokinetic(s), irinotecan, oxaliplatin, fluorouracil, FOLFIRI, FOLFOX, FOLFIRINOX. Only articles displaying nonlinear mixed effect models were included. Study description, pharmacokinetic parameter values and influential covariates are reported. For each model, the typical pharmacokinetic profile was simulated for the standard FOLFIRINOX protocol. The FOLFIRINOX compounds have been studied only separately so far. A total of six articles were retained for 5-fluorouracil, 6 for oxaliplatin and 5 for irinotecan (also including metabolites). Either one- or two-compartment models have been described for 5-fluorouracil, while two- or three-compartment models were reported for oxaliplatin and irinotecan pharmacokinetics. Non-linear elimination was sometimes reported for 5-fluorouracil. Sex and body size were found as influential covariates for all molecules in some publications. Despite some differences in model structures and parameter values, the simulated profiles and subsequent exposure were consistent between studies. The current review allows for a global understanding of FOLFIRINOX pharmacokinetics, and will provide a basis for further development of pharmacokinetics–pharmacodynamics–toxicity models for model-driven FOLFIRINOX protocol optimization to reach the best benefit-to-risk ratio.
- Subjects :
- 0301 basic medicine
Oncology
Cancer Research
FOLFIRINOX
Leucovorin
Toxicology
0302 clinical medicine
FOLFOX
Neoplasms
Antineoplastic Combined Chemotherapy Protocols
Tissue Distribution
MESH: Neoplasms
Pharmacology (medical)
Population pharmacokinetics
Clinical Trials as Topic
education.field_of_study
[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]
3. Good health
Oxaliplatin
MESH: Antineoplastic Combined Chemotherapy Protocols
030220 oncology & carcinogenesis
MESH: Oxaliplatin
FOLFIRI
Fluorouracil
Folfirinox Regimen
medicine.drug
medicine.medical_specialty
MESH: Clinical Trials as Topic
5-Fluorouracil
Population
Antineoplastic Agents
Irinotecan
Nonlinear mixed effect modelling
03 medical and health sciences
Pharmacokinetics
Internal medicine
medicine
Humans
MESH: Irinotecan
MESH: Tissue Distribution
education
Pharmacology
MESH: Humans
business.industry
digestive system diseases
030104 developmental biology
MESH: Antineoplastic Agents
MESH: Leucovorin
business
MESH: Fluorouracil
Subjects
Details
- ISSN :
- 14320843 and 03445704
- Volume :
- 83
- Database :
- OpenAIRE
- Journal :
- Cancer Chemotherapy and Pharmacology
- Accession number :
- edsair.doi.dedup.....d15f49c7b034fc0de036e7e82cca4768