dc.contributor.author | Roda, D | |
dc.contributor.author | Jimenez, B | |
dc.contributor.author | Banerji, U | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2022-06-22T10:19:57Z | |
dc.date.available | 2022-06-22T10:19:57Z | |
dc.date.issued | 2016-05-01 | |
dc.identifier | 1078-0432.CCR-15-1855 | |
dc.identifier.citation | Clinical Cancer Research, 2016, 22 (9), pp. 2127 - 2132 | en_US |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5187 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.doi | 10.1158/1078-0432.CCR-15-1855 | |
dc.description.abstract | Tolerability 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.format | Print-Electronic | |
dc.format.extent | 2127 - 2132 | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | AMER ASSOC CANCER RESEARCH | en_US |
dc.relation.ispartof | Clinical Cancer Research | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Antineoplastic Agents | |
dc.subject | Clinical Trials as Topic | |
dc.subject | Humans | |
dc.subject | Molecular Targeted Therapy | |
dc.subject | Neoplasms | |
dc.subject | Small Molecule Libraries | |
dc.title | Are Doses and Schedules of Small-Molecule Targeted Anticancer Drugs Recommended by Phase I Studies Realistic? | en_US |
dc.type | Journal Article | |
dcterms.dateAccepted | 2015-10-23 | |
dc.date.updated | 2022-06-22T09:46:17Z | |
rioxxterms.version | VoR | en_US |
rioxxterms.versionofrecord | 10.1158/1078-0432.CCR-15-1855 | en_US |
rioxxterms.licenseref.startdate | 2016-05-01 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/26581244 | |
pubs.issue | 9 | |
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-status | Published | |
pubs.volume | 22 | |
icr.researchteam | Clinical Pharmacology | en_US |
dc.contributor.icrauthor | Banerji, Udai | |