title: Impact of surgery on survival in palliative patients with metastatic colorectal cancer after first line treatment with weekly 24-hour infusion of high-dose 5-fluorouracil and folinic acid.
abstract: BACKGROUND
  In palliative first-line treatment of colorectal cancer, the secondary resection of distant metastases after downstaging has constantly gained in importance. The objective of this prospective study was to examine the tumor response rate, the toxicity, the median survival time and the prognostic impact of metastatic resection after downstaging of consecutively enrolled patients with primary nonresectable colorectal cancer treated with once weekly 24-hour (24-h) infusion of high-dose 5-fluorouracil (5-FU) and folinic acid.
  
  
  METHODS
  Between January 1995 and July 1997, 53 consecutive patients with primary nonresectable metastases were recruited for a prospective phase II study. The patients received in out-patient care 500 mg/m2 folinic acid in the form of a 1-2-hour infusion followed by 2600 mg/m2 5-FU administered as a 24-h infusion once weekly. One treatment cycle comprised six weekly infusions followed by a two week rest. Three cycles were administered, and in the event of complete remission (CR) or partial remission (PR) and good tolerability, a fourth cycle was undertaken. Thereafter, the possibility of performing a curative metastatic resection was investigated.
  
  
  RESULTS
  Of the 53 patients treated, 7 showed a CR (13%), 15 patients a PR (28%), 26 patients stable disease (SD) (49%), and 5 patients progressive disease (PD) (10%). As the main symptom of toxicity, diarrhea (CTC grade 3 + 4) was observed in 11 patients (21%), followed by leucocytopenia (CTC grade 3 + 4) in 2 patients (4%), and the hand-foot syndrome in 1 patient (2%). The median survival time was 17 months with a median follow-up of 41 months (range: 28-59 months). In 9 patients (17%), a secondary metastatic resection was considered; in 6 patients (11%) curative resection was performed, and 4 patients (8%) showed no evidence of disease for at least three years.
  
  
  CONCLUSIONS
  In this phase II study, we have been able to show prospectively that, after downstaging by palliative treatment using a weekly 24-h infusion of high-dose 5-FU and folinic acid, secondary curative metastatic resection was technically feasible in 11% of the patients. For some of these patients, long-term survival is therefore possible. Secondary metastatic resection should be carried out in close interdisciplinary cooperation, and should be further investigated in prospective phase III studies.
authors.affiliation: Department of Internal Medicine I, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany. Axel.Wein@med1.imed.uni-erlangen.de
authors.forename: A
authors.initials: A
authors.lastname: Wein
authors.forename: C
authors.initials: C
authors.lastname: Riedel
authors.forename: F
authors.initials: F
authors.lastname: Köckerling
authors.forename: P
authors.initials: P
authors.lastname: Martus
authors.forename: U
authors.initials: U
authors.lastname: Baum
authors.forename: W M
authors.initials: WM
authors.lastname: Brueckl
authors.forename: T
authors.initials: T
authors.lastname: Reck
authors.forename: R
authors.initials: R
authors.lastname: Ott
authors.forename: J
authors.initials: J
authors.lastname: Hänsler
authors.forename: T
authors.initials: T
authors.lastname: Bernatik
authors.forename: D
authors.initials: D
authors.lastname: Becker
authors.forename: T
authors.initials: T
authors.lastname: Schneider
authors.forename: W
authors.initials: W
authors.lastname: Hohenberger
authors.forename: E G
authors.initials: EG
authors.lastname: Hahn
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D007680:Kidney Neoplasms / Q000401:mortality / Q000556:secondary / Q000601:surgery*; D002955:Leucovorin / Q000008:administration & dosage*; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary / Q000601:surgery*; D008175:Lung Neoplasms / Q000401:mortality / Q000556:secondary / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010166:Palliative Care; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D000964:Antimetabolites, Antineoplastic; D002955:Leucovorin; D005472:Fluorouracil