title: Effects of plasma concentrations of 5-fluorouracil on long-term survival after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma.
abstract: BACKGROUND
  A substantial body of literature has accumulated during the past 20 years showing the plasma concentrations of 5-fluorouracil (5-FU) to correlate with clinical response and/or toxicity in colorectal cancer, and head and neck cancer, but little information is available concerning effects on long-term survival. Here, Japanese patients with esophageal squamous cell carcinoma (ESCC) were followed up for 5 years after treatment with a definitive 5-FU/cisplatin (CDDP)-based chemoradiotherapy (CRT), and the association between prognosis and the plasma concentration of 5-FU was evaluated.
  
  
  METHODS
  Forty-nine patients with ESCC, who were treated with a definitive 5-FU/CDDP-based CRT, were enrolled. A course consisted of the continuous infusion of 5-FU at 400 mg/m2/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m2/day on days 1 and 8, and the radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course repeated after a 2-week interval. Plasma concentrations of 5-FU were determined by high performance liquid chromatography at 5:00 PM on days 3, 10, 38 and 45, and at 5:00 AM on days 4, 11, 39 and 46.
  
  
  RESULTS
  The overall 5-year survival rate was 42.9%. Age (P = 0.020), body weight (P = 0.019), and disease stage (P = 0.048) affected the survival, and the survival depended on the clinical response assessed at 1 month after the treatment (P = 0.001). Higher plasma concentrations of 5-FU resulted in a better clinical response (P = 0.043), and trended to prolong survival (P = 0.321).
  
  
  CONCLUSIONS
  The long-term survival after treatment with a definitive 5-FU/CDDP-based CRT possibly depends on the plasma concentrations of 5-FU, and further clinical studies with a larger number of cases are needed to clarify the relationship between them.
authors.affiliation: Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kuwahara
authors.forename: Motohiro
authors.initials: M
authors.lastname: Yamamori
authors.forename: Kaori
authors.initials: K
authors.lastname: Kadoyama
authors.forename: Kohshi
authors.initials: K
authors.lastname: Nishiguchi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Ikuya
authors.initials: I
authors.lastname: Miki
authors.forename: Takao
authors.initials: T
authors.lastname: Tamura
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Okuno
authors.forename: Hideaki
authors.initials: H
authors.lastname: Omatsu
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakaeda
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D044466:Asian People; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000401:mortality / Q000628:therapy*; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D004938:Esophageal Neoplasms / Q000097:blood* / Q000401:mortality / Q000628:therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000097:blood; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D002945:Cisplatin; D005472:Fluorouracil