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dc.contributor.authorAvallone, Antonio
dc.contributor.authorPiccirillo, Maria Carmela
dc.contributor.authorDelrio, Paolo
dc.contributor.authorPecori, Biagio
dc.contributor.authorDi Gennaro, Elena
dc.contributor.authorAloj, Luigi
dc.contributor.authorTatangelo, Fabiana
dc.contributor.authorD'Angelo, Valentina
dc.contributor.authorGranata, Cinzia
dc.contributor.authorCavalcanti, Ernesta
dc.contributor.authorMaurea, Nicola
dc.contributor.authorMaiolino, Piera
dc.contributor.authorBianco, Franco
dc.contributor.authorMontano, Massimo
dc.contributor.authorSilvestro, Lucrezia
dc.contributor.authorTerranova Barberio, Manuela
dc.contributor.authorRoca, Maria Serena
dc.contributor.authorDi Maio, Massimo
dc.contributor.authorMarone, Pietro
dc.contributor.authorBotti, Gerardo
dc.contributor.authorPetrillo, Antonella
dc.contributor.authorDaniele, Gennaro
dc.contributor.authorLastoria, Secondo
dc.contributor.authorIaffaioli, Vincenzo R
dc.contributor.authorRomano, Giovanni
dc.contributor.authorCaracò, Corradina
dc.contributor.authorMuto, Paolo
dc.contributor.authorGallo, Ciro
dc.contributor.authorPerrone, Francesco
dc.contributor.authorBudillon, Alfredo
dc.date.accessioned2018-12-19T00:31:08Z
dc.date.available2018-12-19T00:31:08Z
dc.date.issued2014-11-24
dc.identifier.issn1471-2407
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287180
dc.description.abstractBACKGROUND: Locally advanced rectal cancer (LARC) is a heterogeneous group of tumors where a risk-adapted therapeutic strategy is needed. Short-course radiotherapy (SCRT) is a more convenient option for LARC patients than preoperative long-course RT plus capecitabine. Histone-deacetylase inhibitors (HDACi) have shown activity in combination with RT and chemotherapy in the treatment of solid tumors. Valproic acid (VPA) is an anti-epileptic drug with HDACi and anticancer activity. In preclinical studies, our group showed that the addition of HDACi, including VPA, to capecitabine produces synergistic antitumour effects by up-regulating thymidine phosphorylase (TP), the key enzyme converting capecitabine to 5-FU, and by downregulating thymidylate synthase (TS), the 5-FU target. METHODS/DESIGN: Two parallel phase-1 studies will assess the safety of preoperative SCRT (5 fractions each of 5 Gy, on days 1 to 5) combined with (a) capecitabine alone (increasing dose levels: 500-825 mg/m2/bid), on days 1-21, or (b) capecitabine as above plus VPA (oral daily day -14 to 21, with an intra-patient titration for a target serum level of 50-100 microg/ml) followed by surgery 8 weeks after the end of SCRT, in low-moderate risk RC patients. Also, a randomized phase-2 study will be performed to explore whether the addition of VPA and/or capecitabine to preoperative SCRT might increase pathologic complete tumor regression (TRG1) rate. A sample size of 86 patients (21-22/arm) was calculated under the hypothesis that the addition of capecitabine or VPA to SCRT can improve the TRG1 rate from 5% to 20%, with one-sided alpha = 0.10 and 80% power.Several biomarkers will be evaluated comparing normal mucosa with tumor (TP, TS, VEGF, RAD51, XRCC1, Histones/proteins acetylation, HDAC isoforms) and on blood samples (polymorphisms of DPD, TS, XRCC1, GSTP1, RAD51 and XRCC3, circulating endothelial and progenitors cells; PBMCs-Histones/proteins acetylation). Tumor metabolism will be measured by 18FDG-PET at baseline and 15 days after the beginning of SCRT. DISCUSSION: This project aims to improve the efficacy of preoperative treatment of LARC and to decrease the inconvenience and the cost of standard long-course RT. Correlative studies could identify both prognostic and predictive biomarkers and could add new insight in the mechanism of interaction between VPA, capecitabine and RT.EudraCT Number: 2012-002831-28. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT01898104.
dc.format.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHumans
dc.subjectRectal Neoplasms
dc.subjectValproic Acid
dc.subjectFluorouracil
dc.subjectDeoxycytidine
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectCombined Modality Therapy
dc.subjectPreoperative Care
dc.subjectRadiotherapy
dc.subjectResearch Design
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectYoung Adult
dc.subjectCapecitabine
dc.titlePhase 1/2 study of valproic acid and short-course radiotherapy plus capecitabine as preoperative treatment in low-moderate risk rectal cancer-V-shoRT-R3 (Valproic acid--short Radiotherapy--rectum 3rd trial).
dc.typeArticle
prism.publicationDate2014
prism.publicationNameBMC Cancer
prism.startingPage875
prism.volume14
dc.identifier.doi10.17863/CAM.34489
dcterms.dateAccepted2014-11-13
rioxxterms.versionofrecord10.1186/1471-2407-14-875
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2014-11-24
dc.contributor.orcidAloj, Luigi [0000-0002-7452-4961]
dc.identifier.eissn1471-2407
rioxxterms.typeJournal Article/Review
cam.issuedOnline2014-11-24


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International