title: Second-line treatment of advanced colorectal cancer with a weekly simultaneous 24-hour infusion of 5-fluorouracil and sodium-folinate: a multicentre phase II trial.
abstract: BACKGROUND
  A weekly continuous 24-h infusion therapy with 5-fluorouracil (5-FU) preceded by a 2-h infusion of calcium folinate (CA-FA) was shown to be an effective first- and secondline treatment in advanced metastatic colorectal cancer. Substitution of CA-FA by the new formulation sodium folinate (S-FA) allows the simultaneous i.v. administration of folinic acid with 5-FU in one pump.
  
  
  METHODS
  From 1999 to 2001, 42 patients with metastatic colorectal cancer after pre-treatment with a 5-FU bolus regimen were recruited in 5 centres to receive weekly 24-h infusions of 5-FU (2,600 mg/m2) and S-FA (500 mg/m2) dissolved in one pump for 6 weeks as second-line treatment. The treatment cycle was repeated after a 2-week rest period.
  
  
  RESULTS
  106 6-week cycles (median 2, range 1-6 per patient) were administered during the study. The median followup was 22 months. Out of 42 patients, 1 (2%) achieved complete remission, 3 (7%) partial remission, and 31 (74%) no change. Median time to tumour progression was 5.7 months (95% CI: 4.1-6.5). The median survival was reached at 14.7 months (95% CI: 11.0-22.0). Among major toxicities, NCI-CTC grade III/IV diarrhoea occurred in 8/42 (19%), grade III hand-foot-syndrome in 5/42 (12%) and grade III/IV stomatitis in 3/42 (7%) patients.
  
  
  CONCLUSIONS
  Similar to conventional 24-h 5-FU + CA-FA treatment, the combination with S-FA in second-line therapy induced 9% objective responses and stopped tumour progression in 74%. The simultaneous administration of both, S-FA and 5-FU over 24 h dissolved in one pump is convenient, safe and effective as second-line treatment for patients with colorectal cancer.
authors.affiliation: Klinik für Internistische Onkologie und Hämatologie, Krankenhaus Barmherzige Brüder, Regensburg, Germany. kuhfahl@bayerwaldklinik.de
authors.forename: J
authors.initials: J
authors.lastname: Kuhfahl
authors.forename: C
authors.initials: C
authors.lastname: Steinbrecher
authors.forename: T
authors.initials: T
authors.lastname: Wagner
authors.forename: H
authors.initials: H
authors.lastname: Wagner
authors.forename: D
authors.initials: D
authors.lastname: Fritze
authors.forename: H
authors.initials: H
authors.lastname: Link
authors.forename: F
authors.initials: F
authors.lastname: Schulte
authors.forename: U
authors.initials: U
authors.lastname: Pichlmeier
authors.forename: E-D
authors.initials: ED
authors.lastname: Kreuser
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010166:Palliative Care / Q000379:methods* / Q000706:statistics & numerical data*; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D017670:Sodium Compounds / Q000008:administration & dosage; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D017670:Sodium Compounds; D002955:Leucovorin; D005472:Fluorouracil