title: A randomized phase II study of capecitabine-based chemoradiation with or without bevacizumab in resectable locally advanced rectal cancer: clinical and biological features.
abstract: BACKGROUND
  Perioperatory chemoradiotherapy (CRT) improves local control and survival in patients with locally advanced rectal cancer (LARC). The objective of the current study was to evaluate the addition of bevacizumab (BEV) to preoperative capecitabine (CAP)-based CRT in LARC, and to explore biomarkers for downstaging.
  
  
  METHODS
  Patients (pts) were randomized to receive 5 weeks of radiotherapy 45 Gy/25 fractions with concurrent CAP 825 mg/m(2) twice daily 5 days per week and BEV 5 mg/kg once every 2 weeks (3 doses) (arm A), or the same schedule without BEV (arm B). The primary end point was pathologic complete response (ypCR: ypT0N0).
  
  
  RESULTS
  Ninety pts were included in arm A (44) or arm B (46). Grade 3-4 treatment-related toxicity rates were 16% and 13%, respectively. All patients but one (arm A) proceeded to surgery. The ypCR rate was 16% in arm A and 11% in arm B (p =0.54). Fifty-nine percent vs 39% of pts achieved T-downstaging (arm A vs arm B; p =0.04). Serial samples for biomarker analyses were obtained for 50 out of 90 randomized pts (arm A/B: 22/28). Plasma angiopoietin-2 (Ang-2) levels decreased in arm A and increased in arm B (p <0.05 at all time points). Decrease in Ang-2 levels from baseline to day 57 was significantly associated with tumor downstaging (p =0.02).
  
  
  CONCLUSIONS
  The addition of BEV to CAP-based preoperative CRT has shown to be feasible in LARC. The association between decreasing Ang-2 levels and tumor downstaging should be further validated in customized studies.
  
  
  BACKGROUND
  Clinicaltrials.gov identifier NCT01043484. Trial registration date: 12/30/2009.
authors.affiliation: Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. ramonsalazar@iconcologia.net.
authors.forename: Ramon
authors.initials: R
authors.lastname: Salazar
authors.affiliation: Medical Oncology, Hospital Universitari Vall D'Hebrón, Barcelona, Spain. jacapdevila@vhebron.net.
authors.forename: Jaume
authors.initials: J
authors.lastname: Capdevila
authors.affiliation: Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. blaquente@iconcologia.net.
authors.forename: Berta
authors.initials: B
authors.lastname: Laquente
authors.affiliation: Medical Oncology, Hospital Universitari German Trias I Pujol, Barcelona, Spain. jmanzano@iconcologia.net.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Manzano
authors.affiliation: Medical Oncology, Complejo Sanitario Parc Taulí, Barcelona, Spain. cpericay@gmail.com.
authors.forename: Carles
authors.initials: C
authors.lastname: Pericay
authors.affiliation: Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. mmvillacampa@iconcologia.net.
authors.forename: Mercedes Martínez
authors.initials: MM
authors.lastname: Villacampa
authors.affiliation: Medical Oncology, Hospital Universitario Marqués de Valdecilla, Santander, Spain. clopez@humv.es.
authors.forename: Carlos
authors.initials: C
authors.lastname: López
authors.affiliation: Medical Oncology, Hospital General de L'Hospitalet, Barcelona, Spain. ferran.losa@sanitatintegral.org.
authors.forename: Ferran
authors.initials: F
authors.lastname: Losa
authors.affiliation: Medical Oncology, Hospital General Universitario de Valencia, Valencia, Spain. mjsafont@yahoo.es.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Safont
authors.affiliation: Medical Oncology, Reina Sofía Hospital, University of Córdoba, Maimonides Institute of Biomedical Research (IMIBIC); Spanish Cancer Network (RTICC), Instituto de Salud Carlos III, Córdoba, Spain. magespanya@hotmail.com.
authors.forename: Auxiliadora
authors.initials: A
authors.lastname: Gómez
authors.affiliation: Medical Oncology, Hospital Universitario Miguel Servet, Zaragoza, Spain. valonsoo@salud.aragon.es.
authors.forename: Vicente
authors.initials: V
authors.lastname: Alonso
authors.affiliation: Medical Oncology, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain. pilaresc@gmail.com.
authors.forename: Pilar
authors.initials: P
authors.lastname: Escudero
authors.affiliation: Medical Oncology, Hospital General U. de Elche, Alicante, Spain. j.gallegoplazas@gmail.com.
authors.forename: Javier
authors.initials: J
authors.lastname: Gallego
authors.affiliation: Medical Oncology, Hospital Clínico Universitario San Carlos, Madrid, Spain. jsastrev@salud.madrid.org.
authors.forename: Javier
authors.initials: J
authors.lastname: Sastre
authors.affiliation: Medical Oncology, Hospital Doce de Octubre, Madrid, Spain. cgravalos@telefonica.net.
authors.forename: Cristina
authors.initials: C
authors.lastname: Grávalos
authors.affiliation: General and Digestive Surgery Hospital Universitario de Bellvitge, Barcelona, Spain. sbiondo@bellvitgehospital.cat.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Biondo
authors.affiliation: Radiation Oncology, Hospital Universitario Reina Sofía, Córdoba, Spain. amalia.palacios.sspa@juntadeandalucia.es.
authors.forename: Amalia
authors.initials: A
authors.lastname: Palacios
authors.affiliation: Medical Oncology, Reina Sofía Hospital, University of Córdoba, Maimonides Institute of Biomedical Research (IMIBIC); Spanish Cancer Network (RTICC), Instituto de Salud Carlos III, Córdoba, Spain. earandaa@seom.org.
authors.forename: Enrique
authors.initials: E
authors.lastname: Aranda
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D000069287:Capecitabine / Q000008:administration & dosage* / Q000009:adverse effects; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D057234:Preoperative Period; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D000068258:Bevacizumab; D000069287:Capecitabine