title: Correlation of hypertension and proteinuria with outcome in elderly bevacizumab-treated patients with metastatic colorectal cancer.
abstract: BACKGROUND
  Studies suggest a relationship between hypertension and outcome in bevacizumab-treated patients with metastatic colorectal cancer (mCRC). We performed a retrospective analysis of two phase II studies (BECA and BECOX) to determine if hypertension and proteinuria predict outcome in elderly patients with mCRC treated with bevacizumab.
  
  
  METHODS
  Patients ≥ 70 years of age received either capecitabine 1250 mg/m(2) bid days 1-14 + bevacizumab 7.5 mg/kg day 1 every 21 days (BECA study) or capecitabine 1000 mg/m(2) bid days 1-14 with bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m(2) day 1 (BECOX study). The primary objective was to correlate hypertension and proteinuria with overall response rate (ORR), time to progression (TTP) and overall survival (OS). Secondary objectives included identification of risk factors associated with the development of hypertension and proteinuria and determining whether development of hypertension or proteinuria in the first 2 cycles was related to ORR, disease-control rate (DCR), TTP or OS.
  
  
  RESULTS
  In total, 127 patients (median age 75.5 years) were included in the study. Hypertension correlated with DCR and OS; proteinuria correlated with ORR and DCR. Proteinuria or hypertension in the first 2 cycles did not correlate with efficacy. Risk factors for hypertension were female gender (odds ratio [OR] 0.241; P = 0.011) and more bevacizumab cycles (OR 1.112; P = 0.002); risk factors for proteinuria were diabetes (OR 3.869; P = 0.006) and more bevacizumab cycles (OR 1.181; P<0.0001). Multivariate analysis identified as having prognostic value: baseline lactate dehydrogenase, haemoglobin, number of metastatic lesions and DCR.
  
  
  CONCLUSIONS
  This analysis of two phase II studies suggests that hypertension is significantly correlated with OS but not with ORR and TTP, whereas proteinuria is correlated with ORR but not with OS and TTP. Both hypertension and proteinuria are associated with the duration of bevacizumab treatment and do not represent an independent prognostic factor.
authors.affiliation: Servicio de Oncología Médica, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Feliu
authors.affiliation: Servicio de Oncología Médica, Hospital Arnau de Vilanova, Lleida, Spain.
authors.forename: Antonieta
authors.initials: A
authors.lastname: Salud
authors.affiliation: Servicio de Oncología Médica, Hospital Universitario Clinico de Valencia, Valencia, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Safont
authors.affiliation: Servicio de Oncología Médica, Hospital General Yagüe, Burgos, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: García-Girón
authors.affiliation: Servicio de Oncología Médica, Hospital La Fe de Valencia, Valencia, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Aparicio
authors.affiliation: Servicio de Oncología Médica, Hospital de La Creu Roja de L´Hospitalet, Barcelona, Spain.
authors.forename: Ferran
authors.initials: F
authors.lastname: Losa
authors.affiliation: Servicio de Oncología Médica, Hospital General de Valencia, Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Bosch
authors.affiliation: Servicio de Oncología Médica, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Escudero
authors.affiliation: Servicio de Oncología Médica, Hospital Infanta Sofía, Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Casado
authors.affiliation: Servicio de Oncología Médica, Complejo Hospitalario Xeral Cies, Vigo, Pontevedra, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Jorge
authors.affiliation: Servicio de Oncología Médica, Hospital Universitario de Gran Canaria Doctor Negrin, Las Palmas de Gran Canaria, Spain.
authors.forename: Uriel
authors.initials: U
authors.lastname: Bohn
authors.affiliation: Servicio de Oncología Médica, Hospital Universitario Quiron Madrid, Madrid, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Pérez-Carrión
authors.affiliation: Servicio de Hematología y Oncología Médica, Hospital General Universitario Morales Messeguer, Murcia, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Carmona
authors.affiliation: Servicio de Oncología Médica, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Custodio
authors.affiliation: Servicio de Oncología Médica, Hospital Clinic i Provincial de Barcelona, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Maurel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D000068258:Bevacizumab; D000069287:Capecitabine; D017322:Clinical Trials, Phase II as Topic; D015179:Colorectal Neoplasms / Q000150:complications* / Q000188:drug therapy*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000150:complications*; D008297:Male; D015999:Multivariate Analysis; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin; D011507:Proteinuria / Q000150:complications*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D005472:Fluorouracil