Show simple item record

dc.contributor.authorRoda, D
dc.contributor.authorJimenez, B
dc.contributor.authorBanerji, U
dc.coverage.spatialUnited States
dc.date.accessioned2022-06-22T10:19:57Z
dc.date.available2022-06-22T10:19:57Z
dc.date.issued2016-05-01
dc.identifier1078-0432.CCR-15-1855
dc.identifier.citationClinical Cancer Research, 2016, 22 (9), pp. 2127 - 2132en_US
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5187
dc.identifier.eissn1557-3265
dc.identifier.eissn1557-3265
dc.identifier.doi10.1158/1078-0432.CCR-15-1855
dc.identifier.doi10.1158/1078-0432.CCR-15-1855
dc.description.abstractTolerability of molecularly targeted agents (MTA) used in cancer therapeutics is determined in phase I trials. We reviewed the reported incidence of toxicity in phase III trials at doses and schedules recommended by phase I trials to evaluate whether these recommendations are realistic when drugs are used in larger populations of patients. We systematically reviewed a safety profile of small molecule (SM-MTA) and mAb MTA (MA-MTA) approved by the FDA in the last 12 years. There was a significantly increased percentage of grade 3 or 4 adverse events reported with SM-MTA compared with MA-MTA [40% vs. 27%; RR 1.5; 95% confidence interval (CI), 1.10-2.25, P = 0.038] in phase III studies. Importantly, a substantial proportion of patients (45%) treated with SM-MTA required dose modifications due to drug-related toxicity in phase III trials. However, this toxicity was associated to a definitive study drug discontinuation in only 9%. Overall, 25% of SM-MTA declared recommended phase II doses below MTD based on pharmacokinetic-pharmacodynamic data and these trials were associated with a significantly reduced number of dose modifications in registration trials (32% vs. 50%; RR 0.64; 95% CI, 0.43-0.88, P = 0.01). Tolerability is going to come into further focus due to the need for combinations of SM-MTA and other anticancer agents. There was a higher incidence of grade 3-4 toxicity in phase III trials in combinations versus single-agent SM-MTAs (64% vs. 37%; RR 1.73; 95% CI, 1.3-2.3, P = 0.001). These results indicate that phase I studies underestimate toxicity while recommending doses of SM-MTA. Clin Cancer Res; 22(9); 2127-32. ©2015 AACR.
dc.formatPrint-Electronic
dc.format.extent2127 - 2132
dc.languageeng
dc.language.isoengen_US
dc.publisherAMER ASSOC CANCER RESEARCHen_US
dc.relation.ispartofClinical Cancer Research
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectAntineoplastic Agents
dc.subjectClinical Trials as Topic
dc.subjectHumans
dc.subjectMolecular Targeted Therapy
dc.subjectNeoplasms
dc.subjectSmall Molecule Libraries
dc.titleAre Doses and Schedules of Small-Molecule Targeted Anticancer Drugs Recommended by Phase I Studies Realistic?en_US
dc.typeJournal Article
dcterms.dateAccepted2015-10-23
dc.date.updated2022-06-22T09:46:17Z
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.1158/1078-0432.CCR-15-1855en_US
rioxxterms.licenseref.startdate2016-05-01
rioxxterms.typeJournal Article/Reviewen_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/26581244
pubs.issue9
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Pharmacology – Adaptive Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/The Adult Drug Development Unit at the ICR and the RM
pubs.publication-statusPublished
pubs.volume22
icr.researchteamClinical Pharmacologyen_US
dc.contributor.icrauthorBanerji, Udai


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

http://creativecommons.org/licenses/by/4.0/
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/