title: Adjuvant chemotherapy with folinic acid and 5-fluorouracil in patients with locally advanced rectal cancer previously treated by preoperative radiochemotherapy and curative tumor resection.
abstract: OBJECTIVE
  The role of postoperative adjuvant chemotherapy in patients with rectal cancer pretreated by preoperative radiochemotherapy (RCT) and curative surgery is still poorly investigated.
  
  
  METHODS
  We pooled data from both arms of a phase III trial in which patients with locally advanced (T3/4) rectal cancer were randomized to preoperative RCT alone or combined with pelvic radio-frequency hyperthermia. After surgery, R0-resected patients were scheduled to adjuvant chemotherapy with four monthly courses of 50 mg folinic acid (FA) and gradually escalated 5-fluorouracil (5-FU, 350-500 mg/m2, days 1-5). Reasons preventing initiation of chemotherapy and treatment-related toxicities were evaluated. Patients' characteristics and survival parameters were compared between the treated and untreated patient groups.
  
  
  RESULTS
  Out of 93 patients, 73 (79%) started adjuvant chemotherapy, whereas 19 (21%) did not, mostly due to perioperative complications and refusal. Chemotherapy-related toxicities were mild to moderate in most cases, but--together with protracted postoperative complications--prevented the intended dose escalation of 5-FU in 71% of patients. Distant-failure-free (p=0.03) and overall survival (p=0.03) were improved in the chemotherapy group, although there was a negative selection of patients with unfavourable characteristics into the untreated patient group.
  
  
  CONCLUSIONS
  Adjuvant chemotherapy using FA and 5-FU can be safely applied to the majority of patients with rectal cancer pretreated by RCT and surgery. Survival data are not suitable to allow far-reaching conclusions, but are in line with suggestions of a favourable effect of adjuvant chemotherapy in these patients.
authors.affiliation: Medizinische Klinik für Hämatologie und Onkologie, Charité, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. bert.hildebrandt@charite.de
authors.forename: Bert
authors.initials: B
authors.lastname: Hildebrandt
authors.forename: Beate
authors.initials: B
authors.lastname: Rau
authors.forename: Jürgen
authors.initials: J
authors.lastname: Löffel
authors.forename: Peter
authors.initials: P
authors.lastname: Wust
authors.forename: Annett
authors.initials: A
authors.lastname: Nicolaou
authors.forename: Johanna
authors.initials: J
authors.lastname: Gellermann
authors.forename: Philipp
authors.initials: P
authors.lastname: Le Coutre
authors.forename: Peter
authors.initials: P
authors.lastname: Neuhaus
authors.forename: Roland
authors.initials: R
authors.lastname: Felix
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Wernecke
authors.forename: Bernd
authors.initials: B
authors.lastname: Dörken
authors.forename: Hanno
authors.initials: H
authors.lastname: Riess
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017024:Chemotherapy, Adjuvant; D003082:Colectomy / Q000379:methods*; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D002955:Leucovorin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011182:Postoperative Care / Q000379:methods*; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D014803:Vitamin B Complex; D002955:Leucovorin; D005472:Fluorouracil