Phase 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.contributor.author | Avallone, Antonio | |
dc.contributor.author | Piccirillo, Maria Carmela | |
dc.contributor.author | Delrio, Paolo | |
dc.contributor.author | Pecori, Biagio | |
dc.contributor.author | Di Gennaro, Elena | |
dc.contributor.author | Aloj, Luigi | |
dc.contributor.author | Tatangelo, Fabiana | |
dc.contributor.author | D'Angelo, Valentina | |
dc.contributor.author | Granata, Cinzia | |
dc.contributor.author | Cavalcanti, Ernesta | |
dc.contributor.author | Maurea, Nicola | |
dc.contributor.author | Maiolino, Piera | |
dc.contributor.author | Bianco, Franco | |
dc.contributor.author | Montano, Massimo | |
dc.contributor.author | Silvestro, Lucrezia | |
dc.contributor.author | Terranova Barberio, Manuela | |
dc.contributor.author | Roca, Maria Serena | |
dc.contributor.author | Di Maio, Massimo | |
dc.contributor.author | Marone, Pietro | |
dc.contributor.author | Botti, Gerardo | |
dc.contributor.author | Petrillo, Antonella | |
dc.contributor.author | Daniele, Gennaro | |
dc.contributor.author | Lastoria, Secondo | |
dc.contributor.author | Iaffaioli, Vincenzo R | |
dc.contributor.author | Romano, Giovanni | |
dc.contributor.author | Caracò, Corradina | |
dc.contributor.author | Muto, Paolo | |
dc.contributor.author | Gallo, Ciro | |
dc.contributor.author | Perrone, Francesco | |
dc.contributor.author | Budillon, Alfredo | |
dc.date.accessioned | 2018-12-19T00:31:08Z | |
dc.date.available | 2018-12-19T00:31:08Z | |
dc.date.issued | 2014-11-24 | |
dc.identifier.issn | 1471-2407 | |
dc.identifier.uri | https://www.repository.cam.ac.uk/handle/1810/287180 | |
dc.description.abstract | BACKGROUND: 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.medium | Electronic | |
dc.language | eng | |
dc.publisher | Springer Science and Business Media LLC | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Humans | |
dc.subject | Rectal Neoplasms | |
dc.subject | Valproic Acid | |
dc.subject | Fluorouracil | |
dc.subject | Deoxycytidine | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Combined Modality Therapy | |
dc.subject | Preoperative Care | |
dc.subject | Radiotherapy | |
dc.subject | Research Design | |
dc.subject | Adolescent | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Young Adult | |
dc.subject | Capecitabine | |
dc.title | Phase 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.type | Article | |
prism.publicationDate | 2014 | |
prism.publicationName | BMC Cancer | |
prism.startingPage | 875 | |
prism.volume | 14 | |
dc.identifier.doi | 10.17863/CAM.34489 | |
dcterms.dateAccepted | 2014-11-13 | |
rioxxterms.versionofrecord | 10.1186/1471-2407-14-875 | |
rioxxterms.version | VoR | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2014-11-24 | |
dc.contributor.orcid | Aloj, Luigi [0000-0002-7452-4961] | |
dc.identifier.eissn | 1471-2407 | |
rioxxterms.type | Journal Article/Review | |
cam.issuedOnline | 2014-11-24 |
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