title: Adjuvant radio-chemotherapy in stage II-III rectal cancer with 24-hour infusion of high-dose 5-fluorouracil and folinic acid: evaluation of feasibility.
abstract: BACKGROUND
  Postoperative radio-chemotherapy has been established as standard treatment for stage II and III rectal cancer patients in the last decade. To improve the efficacy of this therapy, we decided to evaluate continuous 24-hour infusion of 5-fluorouracil (5-FU) with folinic acid (FA) in combination with local radiation versus standard bolus 5-FU/FA with local radiation in a randomized study. Here we report on the first 28 patients to receive the experimental treatment.
  
  
  METHODS
  Patients with stage II and III rectal cancer received weekly 2-hour infusions of FA 500 mg/m2 followed by continuous 24-hour infusions of 5-FU 2,600 mg/m2 postoperatively via a Port-A-Cath system. The first cycle included 8 consecutive weekly administrations, the 1st-4th in full dose, the 5th-8th with 50% reduced dose while local irradiation (45 or 50.4 Gy) was performed. Thereafter, two further chemotherapy cycles (6 weekly administrations, 100% dose) followed.
  
  
  RESULTS
  28 patients received continuous 5-FU/FA treatment, of whom only 21 were evaluable for tolerability. 19 patients (90.4%) completed the first cycle, only 14 patients entered the second treatment cycle. Especially during the combined radiochemotherapy, increased toxicity was observed with grade III/IV diarrhea (n = 2), nausea (n = 1), leukopenia (n = 1), and cardiac toxicity (n = 1).
  
  
  CONCLUSIONS
  The high rate of premature treatment dropout indicate that the chosen schedule of weekly high-dose 5-FU/FA continuous infusion and combined postoperative radiotherapy should not be recommended for further use in postoperative adjuvant treatment.
authors.affiliation: Onkologisches Zentrum, III. Medizinische Klinik, Universitätsklinikum Mannheim, Germany. denc@gmx.net
authors.forename: Y
authors.initials: Y
authors.lastname: Dencausse
authors.forename: J
authors.initials: J
authors.lastname: Sturm
authors.forename: G
authors.initials: G
authors.lastname: Hartung
authors.forename: P
authors.initials: P
authors.lastname: Dietzler
authors.forename: L
authors.initials: L
authors.lastname: Edler
authors.forename: M
authors.initials: M
authors.lastname: Bambach
authors.forename: C
authors.initials: C
authors.lastname: Wojatschek
authors.forename: H
authors.initials: H
authors.lastname: Lindemann
authors.forename: W
authors.initials: W
authors.lastname: Qeisser
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010352:Patient Dropouts; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D015996:Survival Rate
chemical_list: D002955:Leucovorin; D005472:Fluorouracil