title: Randomised study of sequential versus combination chemotherapy with capecitabine, irinotecan and oxaliplatin in advanced colorectal cancer, an interim safety analysis. A Dutch Colorectal Cancer Group (DCCG) phase III study.
abstract: BACKGROUND
  Results on overall survival in randomised studies of mono- versus combination chemotherapy in advanced colorectal cancer patients may have been biased by an imbalance in salvage treatments. This is the first randomised study that evaluates sequential versus combination chemotherapy with a fluoropyrimidine, irinotecan and oxaliplatin.
  
  
  METHODS
  A total of 820 patients were randomised between first-line capecitabine, second-line irinotecan and third-line capecitabine + oxaliplatin (arm A) versus first-line capecitabine + irinotecan, and second-line capecitabine + oxaliplatin (arm B). The primary end point was overall survival. We present the results of an interim analysis on the safety data in the first 400 patients.
  
  
  RESULTS
  In first-line the incidence of grade 3-4 diarrhoea, nausea, vomiting and febrile neutropenia was significantly higher in arm B. However, when toxicity over all lines was considered only grade 3 hand-foot syndrome occurred more frequently in arm A (12% versus 6%, respectively, P = 0.041). The incidence of cardiovascular toxicity was low. In two out of five patients with sudden death (one in arm A, four in arm B) cardiovascular risk factors were present.
  
  
  CONCLUSIONS
  Both treatment arms had an acceptable safety profile. These data imply that the results on survival will be the major determinant for the selection of either strategy. Capecitabine plus irinotecan appears to be a feasible first-line treatment for patients with advanced colorectal carcinoma.
authors.affiliation: Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Koopman
authors.forename: N F
authors.initials: NF
authors.lastname: Antonini
authors.forename: J
authors.initials: J
authors.lastname: Douma
authors.forename: J
authors.initials: J
authors.lastname: Wals
authors.forename: A H
authors.initials: AH
authors.lastname: Honkoop
authors.forename: F L G
authors.initials: FL
authors.lastname: Erdkamp
authors.forename: R S
authors.initials: RS
authors.lastname: de Jong
authors.forename: C J
authors.initials: CJ
authors.lastname: Rodenburg
authors.forename: G
authors.initials: G
authors.lastname: Vreugdenhil
authors.forename: J M
authors.initials: JM
authors.lastname: Akkermans-Vogelaar
authors.forename: C J A
authors.initials: CJ
authors.lastname: Punt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000069287:Capecitabine; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D016019:Survival Analysis
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin