Minimally invasive pharmacokinetic and pharmacodynamic technologies in hypothesis-testing clinical trials of innovative therapies.

2.50
Hdl Handle:
http://hdl.handle.net/10541/72717
Title:
Minimally invasive pharmacokinetic and pharmacodynamic technologies in hypothesis-testing clinical trials of innovative therapies.
Authors:
Workman, Paul; Aboagye, E O; Chung, Yuen-Li; Griffiths, John R; Hart, Rachel; Leach, Martin O; Maxwell, Ross J; McSheehy, Paul M J; Price, Patricia M; Zweit, Jamal
Abstract:
Clinical trials of new cancer drugs should ideally include measurements of parameters such as molecular target expression, pharmacokinetic (PK) behavior, and pharmacodynamic (PD) endpoints that can be linked to measures of clinical effect. Appropriate PK/PD biomarkers facilitate proof-of-concept demonstrations for target modulation; enhance the rational selection of an optimal drug dose and schedule; aid decision-making, such as whether to continue or close a drug development project; and may explain or predict clinical outcomes. In addition, measurement of PK/PD biomarkers can minimize uncertainty associated with predicting drug safety and efficacy, reduce the high levels of drug attrition during development, accelerate drug approval, and decrease the overall costs of drug development. However, there are many challenges in the development and implementation of biomarkers that probably explain their disappointingly low implementation in phase I trials. The Pharmacodynamic/Pharmacokinetic Technologies Advisory committee of Cancer Research UK has found that submissions for phase I trials of new cancer drugs in the United Kingdom often lack detailed information about PK and/or PD endpoints, which leads to suboptimal information being obtained in those trials or to delays in starting the trials while PK/PD methods are developed and validated. Minimally invasive PK/PD technologies have logistic and ethical advantages over more invasive technologies. Here we review these technologies, emphasizing magnetic resonance spectroscopy and positron emission tomography, which provide detailed functional and metabolic information. Assays that measure effects of drugs on important biologic pathways and processes are likely to be more cost-effective than those that measure specific molecular targets. Development, validation, and implementation of minimally invasive PK/PD methods are encouraged.
Affiliation:
Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, UK. paul.workman@icr.ac.uk
Citation:
Minimally invasive pharmacokinetic and pharmacodynamic technologies in hypothesis-testing clinical trials of innovative therapies. 2006, 98 (9):580-98 J. Natl. Cancer Inst.
Journal:
Journal of the National Cancer Institute
Issue Date:
3-May-2006
URI:
http://hdl.handle.net/10541/72717
DOI:
10.1093/jnci/djj162
PubMed ID:
16670384
Type:
Article
Language:
en
ISSN:
1460-2105
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorWorkman, Paul-
dc.contributor.authorAboagye, E O-
dc.contributor.authorChung, Yuen-Li-
dc.contributor.authorGriffiths, John R-
dc.contributor.authorHart, Rachel-
dc.contributor.authorLeach, Martin O-
dc.contributor.authorMaxwell, Ross J-
dc.contributor.authorMcSheehy, Paul M J-
dc.contributor.authorPrice, Patricia M-
dc.contributor.authorZweit, Jamal-
dc.date.accessioned2009-07-07T10:44:05Z-
dc.date.available2009-07-07T10:44:05Z-
dc.date.issued2006-05-03-
dc.identifier.citationMinimally invasive pharmacokinetic and pharmacodynamic technologies in hypothesis-testing clinical trials of innovative therapies. 2006, 98 (9):580-98 J. Natl. Cancer Inst.en
dc.identifier.issn1460-2105-
dc.identifier.pmid16670384-
dc.identifier.doi10.1093/jnci/djj162-
dc.identifier.urihttp://hdl.handle.net/10541/72717-
dc.description.abstractClinical trials of new cancer drugs should ideally include measurements of parameters such as molecular target expression, pharmacokinetic (PK) behavior, and pharmacodynamic (PD) endpoints that can be linked to measures of clinical effect. Appropriate PK/PD biomarkers facilitate proof-of-concept demonstrations for target modulation; enhance the rational selection of an optimal drug dose and schedule; aid decision-making, such as whether to continue or close a drug development project; and may explain or predict clinical outcomes. In addition, measurement of PK/PD biomarkers can minimize uncertainty associated with predicting drug safety and efficacy, reduce the high levels of drug attrition during development, accelerate drug approval, and decrease the overall costs of drug development. However, there are many challenges in the development and implementation of biomarkers that probably explain their disappointingly low implementation in phase I trials. The Pharmacodynamic/Pharmacokinetic Technologies Advisory committee of Cancer Research UK has found that submissions for phase I trials of new cancer drugs in the United Kingdom often lack detailed information about PK and/or PD endpoints, which leads to suboptimal information being obtained in those trials or to delays in starting the trials while PK/PD methods are developed and validated. Minimally invasive PK/PD technologies have logistic and ethical advantages over more invasive technologies. Here we review these technologies, emphasizing magnetic resonance spectroscopy and positron emission tomography, which provide detailed functional and metabolic information. Assays that measure effects of drugs on important biologic pathways and processes are likely to be more cost-effective than those that measure specific molecular targets. Development, validation, and implementation of minimally invasive PK/PD methods are encouraged.en
dc.language.isoenen
dc.subjectCanceren
dc.subject.meshAntineoplastic Agents-
dc.subject.meshApoptosis-
dc.subject.meshBiological Markers-
dc.subject.meshBlood Flow Velocity-
dc.subject.meshCell Hypoxia-
dc.subject.meshClinical Trials as Topic-
dc.subject.meshClinical Trials, Phase I as Topic-
dc.subject.meshClinical Trials, Phase II as Topic-
dc.subject.meshHumans-
dc.subject.meshMagnetic Resonance Imaging-
dc.subject.meshMagnetic Resonance Spectroscopy-
dc.subject.meshNeoplasms-
dc.subject.meshPositron-Emission Tomography-
dc.subject.meshRadiopharmaceuticals-
dc.subject.meshSensitivity and Specificity-
dc.subject.meshTomography, X-Ray Computed-
dc.subject.meshUltrasonography-
dc.titleMinimally invasive pharmacokinetic and pharmacodynamic technologies in hypothesis-testing clinical trials of innovative therapies.en
dc.typeArticleen
dc.contributor.departmentCancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, UK. paul.workman@icr.ac.uken
dc.identifier.journalJournal of the National Cancer Instituteen

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