title: Irinotecan plus folinic acid/continuous 5-fluorouracil as simplified bimonthly FOLFIRI regimen for first-line therapy of metastatic colorectal cancer.
abstract: BACKGROUND
  Combination therapy of irinotecan, folinic acid (FA) and 5-fluorouracil (5-FU) has been proven to be highly effective for the treatment of metastatic colorectal cancer. However, in light of safety and efficacy concerns, the best combination regimen for first-line therapy still needs to be defined. The current study reports on the bimonthly FOLFIRI protocol consisting of irinotecan with continuous FA/5-FU in five German outpatient clinics, with emphasis on the safety and efficiency, quality of life, management of delayed diarrhea, and secondary resection of regressive liver metastases.
  
  
  METHODS
  A total of 35 patients were treated for metastatic colorectal cancer. All patients received first-line treatment according to the FOLFIRI regimen, consisting of irinotecan (180 mg/m2), L-FA (200 mg/m2) and 5-FU bolus (400 mg/m2) on day 1, followed by a 46-h continuous infusion 5-FU (2400 mg/m2). One cycle contained three fortnightly administrations. Staging was performed after 2 cycles. Dosage was reduced at any time if toxicity NCI CTC grade III/IV was observed. Chemotherapy was administered only to diarrhea-free patients.
  
  
  RESULTS
  The FOLFIRI regimen was generally well tolerated. It was postponed for one-week in 51 of 415 applications (12.3%). Dose reduction was necessary in ten patients. Grade III/IV toxicity was rare, with diarrhea (14%), nausea/vomiting (12%), leucopenia (3%), neutropenia (9%) and mucositis (3%). The overall response rate was 31% (4 CR and 7 PR), with disease control in 74%. After primary chemotherapy, resection of liver metastases was achieved in three patients. In one patient, the CR was confirmed pathologically. Median progression-free and overall survival were seven and 17 months, respectively.
  
  
  CONCLUSIONS
  The FOLFIRI regimen proved to be safe and efficient. Outpatient treatment was well tolerated. Since downstaging was possible, combinations of irinotecan and continuous FA/5-FU should further be investigated in neoadjuvant protocols.
authors.affiliation: Dept, of Internal Medicine I, Outpatient Unit for GI Cancer, Johannes Gutenberg University, Mainz, Germany. teufel@uni-mainz.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Teufel
authors.forename: Silke
authors.initials: S
authors.lastname: Steinmann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Siebler
authors.forename: Christiane
authors.initials: C
authors.lastname: Zanke
authors.forename: Herbert
authors.initials: H
authors.lastname: Hohl
authors.forename: Bernd
authors.initials: B
authors.lastname: Adami
authors.forename: M
authors.initials: M
authors.lastname: Schroeder
authors.forename: O
authors.initials: O
authors.lastname: Klein
authors.forename: Thomas
authors.initials: T
authors.lastname: Höhler
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.forename: Michael
authors.initials: M
authors.lastname: Heike
authors.forename: Markus
authors.initials: M
authors.lastname: Moehler
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D011788:Quality of Life; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin