title: Phase II study of preoperative bevacizumab, capecitabine and radiotherapy for resectable locally-advanced rectal cancer.
abstract: BACKGROUND
  To evaluate whether the addition of bevacizumab (BVZ) to capecitabine-based chemoradiotherapy in the preoperative treatment of locally advanced rectal cancer (LARC) improves efficacy measured by the pathological complete response (pCR) rate.
  
  
  METHODS
  A phase II two-step design was performed. Patients received four cycles of therapy consisting of: BVZ 10 mg/kg in first infusion on day 1 and 5 mg/kg on days 15, 29, 43, capecitabine 1800 mg/m(2)/day 5 days per week during radiotherapy, which consisted of external-beam irradiation (45 Gy in 1.8 Gy dose per session over 5 sessions/week for 5 weeks). Six to eight weeks after completion of all therapies surgery was undergone. To profile the biological behaviour during BVZ treatment we measured molecular biomarkers before treatment, during BVZ monotherapy, and during and after combination therapy. Microvessel density (MVD) was measured after surgery.
  
  
  RESULTS
  Forty-three patients were assessed and 41 were included in the study. Three patients achieved a pathological complete response (3/40: 7.5%) and 27 (67.5%) had a pathological partial response, (overall pathological response rate of 75%). A further 8 patients (20%) had stable disease, giving a disease control rate of 95%. Downstaging occurred in 31 (31/40: 77.5%) of the patients evaluated. This treatment resulted in an actuarial 4-year disease-free and overall survival of 85.4 and 92.7% respectively. BVZ with chemoradiotherapy showed acceptable toxicity. No correlations were observed between biomarker results and efficacy variables.
  
  
  CONCLUSIONS
  BVZ with capecitabine and radiotherapy seem safe and active and produce promising survival results in LARC.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier NCT00847119 . Trial registration date: February 18, 2009.
authors.affiliation: Clinical Research Unit, Institut Català d'Oncologia, Avinguda Gran Via de l'Hospitalet, 199-203 08907 L'Hospitalet de Llobregat, Barcelona, Spain. mgarciamartin@iconcologia.net.
authors.forename: Margarita
authors.initials: M
authors.lastname: García
authors.affiliation: Department of Medical Oncology, Institut Català d'Oncologia-IDIBELL, L'Hospitalet, Barcelona, Spain. mmvillacampa@iconcologia.net.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Martinez-Villacampa
authors.affiliation: Department of Medical Oncology, Institut Català d'Oncologia-IDIBELL, L'Hospitalet, Barcelona, Spain. csantos@iconcologia.net.
authors.forename: Cristina
authors.initials: C
authors.lastname: Santos
authors.affiliation: Clinical Research Unit, Institut Català d'Oncologia, Avinguda Gran Via de l'Hospitalet, 199-203 08907 L'Hospitalet de Llobregat, Barcelona, Spain. vnavarro@iconcologia.net.
authors.forename: Valentin
authors.initials: V
authors.lastname: Navarro
authors.affiliation: Department of Medical Oncology, Institut Català d'Oncologia-IDIBELL, L'Hospitalet, Barcelona, Spain. ateule@iconcologia.net.
authors.forename: Alex
authors.initials: A
authors.lastname: Teule
authors.affiliation: Department of Medical Oncology, Hospital General de L'Hospitalet, Barcelona, Spain. ferran.losa@sanitatintegral.org.
authors.forename: Ferran
authors.initials: F
authors.lastname: Losa
authors.affiliation: Department of Medical Oncology, Institut Català d'Oncologia-IDIBELL, L'Hospitalet, Barcelona, Spain. apisa@tauli.cat.
authors.forename: Aleydis
authors.initials: A
authors.lastname: Pisa
authors.affiliation: Department of Radiotherapy, Institut Català d'Oncologia-IDIBELL, L'Hospitalet, Barcelona, Spain. mcambray@iconcologia.net.
authors.forename: Maria
authors.initials: M
authors.lastname: Cambray
authors.affiliation: Department of Medical Oncology, Institut Català d'Oncologia-IDIBELL, L'Hospitalet, Barcelona, Spain. gsoler@iconcologia.net.
authors.forename: Gemma
authors.initials: G
authors.lastname: Soler
authors.affiliation: Department of Medical Oncology, Institut Català d'Oncologia-IDIBELL, L'Hospitalet, Barcelona, Spain. laura.lema@gmail.com.
authors.forename: Laura
authors.initials: L
authors.lastname: Lema
authors.affiliation: Department of Surgery, Hospital Universitario de Bellvitge -IDIBELL, L'Hospitalet, Barcelona, Spain. ekreisler@bellvitgehospital.cat.
authors.forename: Esther
authors.initials: E
authors.lastname: Kreisler
authors.affiliation: Translational Research Laboratory, Institut Català d'Oncologia-IDIBELL, L'Hospitalet, Barcelona, Spain. afigueras@iconcologia.net.
authors.forename: Agnes
authors.initials: A
authors.lastname: Figueras
authors.affiliation: Department of Pathology, Hospital Universitario de Bellvitge -IDIBELL, L'Hospitalet, Barcelona, Spain. sanjuan@bellvitgehospital.cat.
authors.forename: Xavier San
authors.initials: XS
authors.lastname: Juan
authors.affiliation: Translational Research Laboratory, Institut Català d'Oncologia-IDIBELL, L'Hospitalet, Barcelona, Spain. fvinyals@iconcologia.net.
authors.forename: Francesc
authors.initials: F
authors.lastname: Viñals
authors.affiliation: Department of Surgery, Hospital Universitario de Bellvitge -IDIBELL, L'Hospitalet, Barcelona, Spain. sbiondo@bellvitgehospital.cat.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Biondo
authors.affiliation: Department of Medical Oncology, Institut Català d'Oncologia-IDIBELL, L'Hospitalet, Barcelona, Spain. ramonsalazar@iconcologia.net.
authors.forename: Ramon
authors.initials: R
authors.lastname: Salazar
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000627:therapeutic use; D000069287:Capecitabine / Q000008:administration & dosage* / Q000627:therapeutic use; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods*; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D057234:Preoperative Period; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000068258:Bevacizumab; D000069287:Capecitabine