title: Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study.
abstract: OBJECTIVE
  This phase III study compared the safety and efficacy of the following three different irinotecan-containing regimens in the first-line treatment of metastatic colorectal cancer: irinotecan plus infusional fluorouracil (FU)/leucovorin (LV) (FOLFIRI), irinotecan plus bolus FU/LV (mIFL), and irinotecan plus oral capecitabine (CapeIRI).
  
  
  METHODS
  A total of 430 previously untreated metastatic colorectal cancer patients were randomly assigned to receive FOLFIRI (n = 144), mIFL (n = 141), or CapeIRI (n = 145). Patients were concurrently randomly assigned to a double-blind treatment with celecoxib or placebo. After a protocol amendment, an additional 117 patients were randomly assigned to either FOLFIRI plus bevacizumab (FOLFIRI+Bev; n = 57) or mILF plus bevacizumab (mIFL+Bev; n = 60), whereas the CapeIRI arm was discontinued. The primary study end point was progression-free survival (PFS), with secondary end points of overall survival (OS), response rate, and toxicity.
  
  
  RESULTS
  Median PFS was 7.6 months for FOLFIRI, 5.9 months for mIFL (P = .004 for the comparison with FOLFIRI), and 5.8 months for CapeIRI (P = .015). Median OS was 23.1 months for FOLFIRI, 17.6 months for mIFL (P = .09), and 18.9 months for CapeIRI (P = .27). CapeIRI was associated with higher rates of severe vomiting, diarrhea, and dehydration. After the amendment to add bevacizumab, the median survival time has not yet been reached for FOLFIRI+Bev and was 19.2 months for mIFL+Bev (P = .007). FOLFIRI+Bev was associated with a higher rate of > or = grade 3 hypertension than mIFL+Bev.
  
  
  CONCLUSIONS
  FOLFIRI and FOLFIRI+Bev offered superior activity to their comparators and were comparably safe. An infusional schedule of FU should be the preferred irinotecan-based regimen in first-line metastatic colorectal cancer.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA 02115, USA. charles_fuchs@dfci.harvard.edu
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.forename: John
authors.initials: J
authors.lastname: Marshall
authors.forename: Edith
authors.initials: E
authors.lastname: Mitchell
authors.forename: Rafal
authors.initials: R
authors.lastname: Wierzbicki
authors.forename: Vinod
authors.initials: V
authors.lastname: Ganju
authors.forename: Mark
authors.initials: M
authors.lastname: Jeffery
authors.forename: Joseph
authors.initials: J
authors.lastname: Schulz
authors.forename: Donald
authors.initials: D
authors.lastname: Richards
authors.forename: Raoudha
authors.initials: R
authors.lastname: Soufi-Mahjoubi
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wang
authors.forename: José
authors.initials: J
authors.lastname: Barrueco
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D003841:Deoxycytidine; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin