dc.contributor.author | Sclafani, F | |
dc.contributor.author | Kim, TY | |
dc.contributor.author | Cunningham, D | |
dc.contributor.author | Kim, TW | |
dc.contributor.author | Tabernero, J | |
dc.contributor.author | Schmoll, HJ | |
dc.contributor.author | Roh, JK | |
dc.contributor.author | Kim, SY | |
dc.contributor.author | Park, YS | |
dc.contributor.author | Guren, TK | |
dc.contributor.author | Hawkes, E | |
dc.contributor.author | Clarke, SJ | |
dc.contributor.author | Ferry, D | |
dc.contributor.author | Frodin, J-E | |
dc.contributor.author | Ayers, M | |
dc.contributor.author | Nebozhyn, M | |
dc.contributor.author | Peckitt, C | |
dc.contributor.author | Loboda, A | |
dc.contributor.author | Watkins, DJ | |
dc.date.accessioned | 2017-08-18T09:00:56Z | |
dc.date.issued | 2017-01 | |
dc.identifier.citation | International journal of cancer, 2017, 140 (2), pp. 431 - 439 | |
dc.identifier.issn | 0020-7136 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/785 | |
dc.identifier.eissn | 1097-0215 | |
dc.identifier.doi | 10.1002/ijc.30453 | |
dc.description.abstract | Limited data are available on the efficacy of anti-IGF-1R agents in KRAS mutant colorectal cancer (CRC). We analysed the outcome of 69 chemorefractory, KRAS exon 2 mutant CRC patients who were enrolled in a double-blind, randomised, phase II/III study of irinotecan and cetuximab plus dalotuzumab 10 mg/kg once weekly (arm A), dalotuzumab 7.5 mg/kg every second week (arm B) or placebo (arm C). Objective response rate (5.6% vs. 3.1% vs. 4.8%), median progression-free survival (2.7 vs. 2.6 vs. 1.4 months) and overall survival (7.8 vs. 10.3 vs. 7.8 months) were not statistically significantly different between treatment groups. Most common grade ≥3 treatment-related toxicities included neutropenia, diarrhoea, hyperglycaemia, fatigue and dermatitis acneiform. Expression of IGF-1R, IGF-1, IGF-2 and EREG by quantitative real-time polymerase chain reaction was assessed in 351 patients from the same study with available data on KRAS exon 2 mutational status. Median cycle threshold values for all biomarkers were significantly lower (i.e., higher expression, p < 0.05) among patients with KRAS wild-type compared to those with KRAS exon 2 mutant tumours. No significant changes were found according to location of the primary tumour with only a trend towards lower expression of IGF-1 in colon compared to rectal cancers (p = 0.06). Albeit limited by the small sample size, this study does not appear to support a potential role for anti-IGF-1R agents in KRAS exon 2 mutant CRC. Data on IGF-1R, IGF-1 and IGF-2 expression here reported may be useful for patient stratification in future trials with inhibitors of the IGF pathway. | |
dc.format | Print-Electronic | |
dc.format.extent | 431 - 439 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
dc.subject | Humans | |
dc.subject | Colorectal Neoplasms | |
dc.subject | Camptothecin | |
dc.subject | Receptor, IGF Type 1 | |
dc.subject | Insulin-Like Growth Factor I | |
dc.subject | Insulin-Like Growth Factor II | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Antibodies, Monoclonal | |
dc.subject | Disease-Free Survival | |
dc.subject | Double-Blind Method | |
dc.subject | Mutation | |
dc.subject | Exons | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Proto-Oncogene Proteins p21(ras) | |
dc.subject | Antibodies, Monoclonal, Humanized | |
dc.subject | Cetuximab | |
dc.subject | Irinotecan | |
dc.title | Dalotuzumab in chemorefractory KRAS exon 2 mutant colorectal cancer: Results from a randomised phase II/III trial. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-08-19 | |
rioxxterms.versionofrecord | 10.1002/ijc.30453 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2017-01 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | International journal of cancer | |
pubs.issue | 2 | |
pubs.notes | 12 months | |
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/Medicine (RMH Smith Cunningham) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.) | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
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/Medicine (RMH Smith Cunningham) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.) | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.volume | 140 | en_US |
pubs.embargo.terms | 12 months | |
icr.researchteam | Medicine (RMH Smith Cunningham) | en_US |
dc.contributor.icrauthor | Cunningham, David | en |
dc.contributor.icrauthor | Marsden, | en |