EO9 (Apaziquone): from the clinic to the laboratory and back again

EO9 (Apaziquone) is a bioreductive drug that has a chequered history. It underwent clinical trial but failed to show activity in phase II clinical trials when administered i.v. Poor drug delivery to tumours caused by a combination of rapid pharmacokinetic elimination and poor penetration through ava...

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Published inBritish journal of pharmacology Vol. 168; no. 1; pp. 11 - 18
Main Authors Phillips, Roger M, Hendriks, Hans R, Peters, Godefridus J
Format Journal Article
LanguageEnglish
Published Oxford, UK Blackwell Publishing Ltd 01.01.2013
Subjects
Administration, Intravesical
Animals
Antineoplastic Agents - pharmacokinetics
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Apaziquone
Area Under Curve
Aziridines - pharmacology
bioreductive prodrugs
bladder cancer
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Transitional Cell - drug therapy
Carcinoma, Transitional Cell - pathology
Clinical trials
Disease Models, Animal
Drug Delivery Systems
EO9
Eoquin
Humans
hypoxia
Immunohistochemistry
Indolequinones - pharmacology
Lung Neoplasms - drug therapy
NQO1
Pharmaceutical industry
Reviews
Treatment Failure
Urinary Bladder - drug effects
Urinary Bladder - pathology
Urinary Bladder Neoplasms - drug therapy
Urinary Bladder Neoplasms - pathology
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Abstract EO9 (Apaziquone) is a bioreductive drug that has a chequered history. It underwent clinical trial but failed to show activity in phase II clinical trials when administered i.v. Poor drug delivery to tumours caused by a combination of rapid pharmacokinetic elimination and poor penetration through avascular tissue were the major factors responsible for EO9's poor efficacy. Based upon an understanding of why EO9 failed, a further clinical trial against patients with superficial transitional cell carcinoma of the bladder was conducted. The rationale for this was that intravesical administration directly into the bladder would circumvent the drug delivery problem, and any drug reaching the blood supply would be rapidly cleared thereby reducing the risk of systemic exposure. EO9 was well tolerated, and clinical activity against marker lesions was recorded in both phase I and II clinical trials. This article charts the pharmacological history of EO9 and discusses the potential implications that ‘the EO9 story’ has for the development of other loco‐regional therapies.
AbstractList EO9 (Apaziquone) is a bioreductive drug that has a chequered history. It underwent clinical trial but failed to show activity in phase II clinical trials when administered i.v. Poor drug delivery to tumours caused by a combination of rapid pharmacokinetic elimination and poor penetration through avascular tissue were the major factors responsible for EO9's poor efficacy. Based upon an understanding of why EO9 failed, a further clinical trial against patients with superficial transitional cell carcinoma of the bladder was conducted. The rationale for this was that intravesical administration directly into the bladder would circumvent the drug delivery problem, and any drug reaching the blood supply would be rapidly cleared thereby reducing the risk of systemic exposure. EO9 was well tolerated, and clinical activity against marker lesions was recorded in both phase I and II clinical trials. This article charts the pharmacological history of EO9 and discusses the potential implications that 'the EO9 story' has for the development of other loco-regional therapies.EO9 (Apaziquone) is a bioreductive drug that has a chequered history. It underwent clinical trial but failed to show activity in phase II clinical trials when administered i.v. Poor drug delivery to tumours caused by a combination of rapid pharmacokinetic elimination and poor penetration through avascular tissue were the major factors responsible for EO9's poor efficacy. Based upon an understanding of why EO9 failed, a further clinical trial against patients with superficial transitional cell carcinoma of the bladder was conducted. The rationale for this was that intravesical administration directly into the bladder would circumvent the drug delivery problem, and any drug reaching the blood supply would be rapidly cleared thereby reducing the risk of systemic exposure. EO9 was well tolerated, and clinical activity against marker lesions was recorded in both phase I and II clinical trials. This article charts the pharmacological history of EO9 and discusses the potential implications that 'the EO9 story' has for the development of other loco-regional therapies.
EO9 (Apaziquone) is a bioreductive drug that has a chequered history. It underwent clinical trial but failed to show activity in phase II clinical trials when administered i.v. Poor drug delivery to tumours caused by a combination of rapid pharmacokinetic elimination and poor penetration through avascular tissue were the major factors responsible for EO9's poor efficacy. Based upon an understanding of why EO9 failed, a further clinical trial against patients with superficial transitional cell carcinoma of the bladder was conducted. The rationale for this was that intravesical administration directly into the bladder would circumvent the drug delivery problem, and any drug reaching the blood supply would be rapidly cleared thereby reducing the risk of systemic exposure. EO9 was well tolerated, and clinical activity against marker lesions was recorded in both phase I and II clinical trials. This article charts the pharmacological history of EO9 and discusses the potential implications that ‘the EO9 story’ has for the development of other loco‐regional therapies.
EO9 (Apaziquone) is a bioreductive drug that has a chequered history. It underwent clinical trial but failed to show activity in phase II clinical trials when administered i.v. Poor drug delivery to tumours caused by a combination of rapid pharmacokinetic elimination and poor penetration through avascular tissue were the major factors responsible for EO9's poor efficacy. Based upon an understanding of why EO9 failed, a further clinical trial against patients with superficial transitional cell carcinoma of the bladder was conducted. The rationale for this was that intravesical administration directly into the bladder would circumvent the drug delivery problem, and any drug reaching the blood supply would be rapidly cleared thereby reducing the risk of systemic exposure. EO9 was well tolerated, and clinical activity against marker lesions was recorded in both phase I and II clinical trials. This article charts the pharmacological history of EO9 and discusses the potential implications that 'the EO9 story' has for the development of other loco-regional therapies. [PUBLICATION ABSTRACT]
Author Hendriks, Hans R
Peters, Godefridus J
Phillips, Roger M
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  surname: Peters
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/22509926$$D View this record in MEDLINE/PubMed
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Snippet EO9 (Apaziquone) is a bioreductive drug that has a chequered history. It underwent clinical trial but failed to show activity in phase II clinical trials when...
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SubjectTerms Administration, Intravesical
Animals
Antineoplastic Agents - pharmacokinetics
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Apaziquone
Area Under Curve
Aziridines - pharmacology
bioreductive prodrugs
bladder cancer
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Transitional Cell - drug therapy
Carcinoma, Transitional Cell - pathology
Clinical trials
Disease Models, Animal
Drug Delivery Systems
EO9
Eoquin
Humans
hypoxia
Immunohistochemistry
Indolequinones - pharmacology
Lung Neoplasms - drug therapy
NQO1
Pharmaceutical industry
Reviews
Treatment Failure
Urinary Bladder - drug effects
Urinary Bladder - pathology
Urinary Bladder Neoplasms - drug therapy
Urinary Bladder Neoplasms - pathology
Title EO9 (Apaziquone): from the clinic to the laboratory and back again
URI https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fj.1476-5381.2012.01996.x
https://www.ncbi.nlm.nih.gov/pubmed/22509926
https://www.proquest.com/docview/1528616575
https://www.proquest.com/docview/1284289283
https://pubmed.ncbi.nlm.nih.gov/PMC3569998
Volume 168
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