title: Efficacy and safety of cetuximab/irinotecan in chemotherapy-refractory metastatic colorectal adenocarcinomas: a clinical practice setting, multicenter experience.
abstract: BACKGROUND
  This study was designed to evaluate the efficacy and safety of irinotecan/cetuximab administered as third- or fourth-line therapy in a retrospective series of patients with metastatic colorectal cancer refractory to oxaliplatin and irinotecan.
  
  
  METHODS
  Most patients (90%) had been previously treated with adjuvant 5-fluorouracil/leucovorin, and all had received oxaliplatin-based regimens before receiving irinotecan-based second-line treatment. Sixty patients with irinotecan-refractory colorectal cancer received a regimen comprising weekly irinotecan 120 mg/m2 as a 1-hour intravenous infusion and cetuximab 400 mg/m2 infused over 2 hours as the initial dose and 250 mg/m2 infused over 1 hour for the subsequent administrations. A single treatment cycle comprised 4 weekly infusions followed by 2 weeks of rest.
  
  
  RESULTS
  According to an intent-to-treat analysis, a partial response was exhibited in 12 of 60 enrolled patients (20%; 95% confidence interval, 11%-32%) with a median duration of 5.1 months (range, 3-7.4 months). The tumor growth control rate was 50% (95% confidence interval, 37%-63%). Objective responses did not correlate with performance status, number of sites of disease, and pretreatments or epidermal growth factor receptor status. The median progression-free survival was 3.1 months (range, 1.2-9 months), whereas median overall survival was 6 months (range, 2-13 months). Both survival parameters correlated with performance status at the beginning of treatment. The main grade 3/4 toxicities were nausea (33%), diarrhea (27%), leukopenia (18%), asthenia (13%), and acne-like reaction (13%).
  
  
  CONCLUSIONS
  Our data suggest that the weekly irinotecan/cetuximab regimen is feasible in an outpatient setting and tolerated by most patients. At present, combinations of chemotherapy with cetuximab are being evaluated in patients with earlier-stage disease in a number of ongoing studies.
authors.affiliation: Department of Experimental Oncology and Clinical Applications, University of Palermo, and Medical Oncology Unit, Ospedale San Giovanni di Dio, Napoli, Italy. vittorio.gebbia@tin.it
authors.forename: Vittorio
authors.initials: V
authors.lastname: Gebbia
authors.forename: Salvatore
authors.initials: S
authors.lastname: Del Prete
authors.forename: Nicolò
authors.initials: N
authors.lastname: Borsellino
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferraù
authors.forename: Paolo
authors.initials: P
authors.lastname: Tralongo
authors.forename: Francesco
authors.initials: F
authors.lastname: Verderame
authors.forename: Vita
authors.initials: V
authors.lastname: Leonardi
authors.forename: Elena
authors.initials: E
authors.lastname: Capasso
authors.forename: Evaristo
authors.initials: E
authors.lastname: Maiello
authors.forename: Roberto
authors.initials: R
authors.lastname: Bordonaro
authors.forename: Sergio
authors.initials: S
authors.lastname: Stinco
authors.forename: Biagio
authors.initials: B
authors.lastname: Agostara
authors.forename: Carlo
authors.initials: C
authors.lastname: Barone
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000077146:Irinotecan; D066246:ErbB Receptors; D000068818:Cetuximab; D002166:Camptothecin