title: A phase II study of high-dose cetuximab plus irinotecan in colorectal cancer patients with KRAS wild-type tumors who progressed after standard dose of cetuximab plus irinotecan.
abstract: OBJECTIVE
  We conducted a phase II clinical trial of high-dose cetuximab plus irinotecan in KRAS wild-type patients who progressed on standard-dose cetuximab plus irinotecan.
  
  
  METHODS
  Patients who progressed within 4 weeks from receiving a minimum of 6 weeks of standard-dose cetuximab plus irinotecan were included in this study. Cetuximab was administered at 500 mg/m(2)/week and irinotecan was administered at the same dose/schedule on which each individual patient had previously progressed. The study was closed early after having met its primary end point.
  
  
  RESULTS
  Twenty patients were treated. The regimen was found to be efficacious, with 9 patients achieving disease control lasting more than 12 weeks. The median progression-free survival and overall survival were 2.8 and 6.6 months, respectively. The toxicity profile was favorable, with the exception of grade 3-4 hypomagnesemia which was noted in 25% of patients.
  
  
  CONCLUSIONS
  High-dose cetuximab plus irinotecan rechallenge can re-elicit clinical benefits in patients who have previously failed cetuximab plus irinotecan treatment. The clinical benefits are modest and may be related to cetuximab rechallenge rather than cetuximab dose escalation.
authors: Roswell Park Cancer Institute, Buffalo, NY, USA.
authors: Ahmad A
authors: AA
authors: Fora
authors: Jeanne A
authors: JA
authors: McMahon
authors: Greg
authors: G
authors: Wilding
authors: Adrienne
authors: A
authors: Groman
authors: Wen Wee
authors: WW
authors: Ma
authors: Karen S
authors: KS
authors: Romano
authors: Marwan G
authors: MG
authors: Fakih
mesh_terms: 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*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000077146:Irinotecan; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002166:Camptothecin