title: A triplet combination with irinotecan (CPT-11), oxaliplatin (LOHP), continuous infusion 5-fluorouracil and leucovorin (FOLFOXIRI) plus cetuximab as first-line treatment in KRAS wt, metastatic colorectal cancer: a pilot phase II trial.
abstract: BACKGROUND
  We conducted an open-label, pilot phase II trial to evaluate the efficacy and safety of FOLFOXIRI plus cetuximab as first-line treatment of patients with metastatic colorectal cancer (mCRC).
  
  
  METHODS
  Thirty patients with KRAS wild-type mCRC, <70 years and with performance status 0-1 were included in the trial.
  
  
  RESULTS
  Complete and partial responses were observed in 4 (13.3%) and 17 (56.7%) patients, respectively (overall response rate (ORR)=70%; 95% confidence interval (CI): 53.6%-86.4%); 8 patients (26.7%) had stable disease and 1 had progressive disease. The median time to tumour progression was 10.2 months (95% CI: 7.1-13.4) and the overall median survival time was 30.3 months (95% CI: 18.8-41.9). Secondary R0 resection was performed in 11 (37%) patients. Grade 3 or 4 diarrhoea and neutropenia were observed in 16 (53%) and 7 (23.3%) patients, respectively, and febrile neutropenia observed in 2 (6.6%) patients. Neurotoxicity grade 2 or 3 was reported in 7 (23.3%) and in 2 (6.7%) patients, respectively, and grade 3 rush was reported in 1 patient.
  
  
  CONCLUSIONS
  The FOLFOXIRI/cetuximab combination presented increased activity in terms of response rate and R0 secondary liver metastases resection, and merits further investigation, especially in patients with initially unresectable disease confined to the liver.
authors.affiliation: Laboratory of Tumor Cell Biology School of Medicine, University of Crete, Heraklion, Greece.
authors.forename: Z
authors.initials: Z
authors.lastname: Saridaki
authors.forename: N
authors.initials: N
authors.lastname: Androulakis
authors.forename: N
authors.initials: N
authors.lastname: Vardakis
authors.forename: L
authors.initials: L
authors.lastname: Vamvakas
authors.forename: E
authors.initials: E
authors.lastname: Kabouraki
authors.forename: K
authors.initials: K
authors.lastname: Kalbakis
authors.forename: D
authors.initials: D
authors.lastname: Hatzidaki
authors.forename: A
authors.initials: A
authors.lastname: Voutsina
authors.forename: D
authors.initials: D
authors.lastname: Mavroudis
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
authors.forename: J
authors.initials: J
authors.lastname: Souglakos
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006498:Hepatectomy; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008113:Liver Neoplasms / Q000556:secondary / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D010865:Pilot Projects; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras); D016896:Treatment Outcome; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin