title: Impact of C-reactive protein kinetics on survival of patients with advanced urothelial carcinoma treated by second-line chemotherapy with gemcitabine, etoposide and cisplatin.
abstract: OBJECTIVE
  To assess the impact of C-reactive protein (CRP) kinetics, the effect of dynamic changes of CRP concentration on the survival of patients with locally advanced or metastatic urothelial carcinoma (UC) treated by single chemotherapeutic regimen including cisplatin was examined.
  
  
  METHODS
  Eighty patients with advanced UC, who failed treatment of advanced UC with the first-line chemotherapy or who received perioperative treatment of neoadjuvant or adjuvant settings, were treated with gemcitabine, etoposide and cisplatin (GEP) as second-line chemotherapy. Patients were divided into three groups according to CRP kinetics based on baseline and nadir CRP concentrations. Patients whose baseline CRP levels were <5 mg/L, patients whose baseline CRP levels were ≥5 mg/L and normalized (<5 mg/L), and patients whose baseline CRP levels were ≥5 mg/L and never normalized were assigned to non-elevated, normalized and non-normalized CRP groups, respectively. The prognostic impact of CRP kinetics and the correlation between normalized CRP period and overall survival period were determined.
  
  
  RESULTS
  In 46 (57%) of the 80 patients, CRP levels were elevated at the diagnosis of advanced UC. During treatment, after a median follow-up period of 12 months CRP levels were normalized in 24 (71%) of 34 patients, whereas CRP levels remained elevated in the remaining 10 patients. Overall survival rates were significantly different between the non-elevated, normalized, and non-normalized CRP groups (P < 0.001), with 1-year survival rates of 72, 51 and 14%, respectively. On multivariate analysis including Eastern Cooperative Oncology Group performance status, visceral metastasis, number of metastatic sites, previous definitive surgery, anaemia, baseline and nadir CRP levels (mg/L), and CRP kinetics status, CRP kinetics was an independent and significant factor for overall survival. The normalized CRP period was significantly correlated with the overall survival period in 52 patients who died.
  
  
  CONCLUSIONS
  CRP kinetics is significantly associated with the prognosis and survival period of patients with advanced UC treated by chemotherapy. Although larger confirmatory studies are warranted to validate our results, CRP can potentially be a useful biomarker for patients with advanced UC.
authors.affiliation: Department of Urology, Cancer Institute Hospital, Japanese Foundation of Cancer Research, Tokyo, Japan. kz-saito.uro@tmd.ac.jp
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Saito
authors.forename: Shinji
authors.initials: S
authors.lastname: Urakami
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Komai
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Yasuda
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kubo
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kitsukawa
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Okubo
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Junji
authors.initials: J
authors.lastname: Yonese
authors.forename: Iwao
authors.initials: I
authors.lastname: Fukui
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D002097:C-Reactive Protein / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D003841:Deoxycytidine; D005047:Etoposide; D002097:C-Reactive Protein; D002945:Cisplatin; D000093542:Gemcitabine