title: Phase II study of irinotecan and cetuximab given every 2 weeks as second-line therapy for advanced colorectal cancer.
abstract: BACKGROUND
  Irinotecan and weekly cetuximab (I+C) is a standard second-line regimen for metastatic colorectal cancer (mCRC). This study investigated the safety and efficacy of every 2 weeks I+C in patients with mCRC.
  
  
  METHODS
  Patients with mCRC refractory to first-line fluoropyrimidine/oxaliplatin regimens and not previously treated with I+C were eligible. Response rate (RR) was the primary endpoint. Cetuximab 500 mg/m(2) and irinotecan 180 mg/m(2) were administered intravenously (I.V.) on day 1 every 2 weeks.
  
  
  RESULTS
  Patient characteristics (n = 31): male (n = 17), median age 62; Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1 (n = 30), and PS = 2 (n = 1). Median number of cycles = 3 (range, 1-22). I+C doses were modified in 18 and 12 patients, respectively. Grade 3/4 adverse events: acneiform rash (n = 6); neutropenia (n = 6); and diarrhea (n = 5); there was one grade 5 respiratory failure, possibly related to therapy. Two patients had a partial response, 11 had stable disease, and 18 had progressive disease resulting in an overall RR of 6% and disease control rate of 41.9%. Median overall survival (OS) was 9.3 months (95% CI, 5.1-15), and time to progression (TTP) was 2.4 months (95% CI, 1.3-4.6). K-ras and BRAF mutations were detected in 39% and 9%, respectively, of the patients tested. There was a trend toward longer TTP among patients with wild-type K-ras and BRAF (2.6 vs. 1.7 months; P = 0.16), and OS was significantly longer in those patients (14.1 vs. 5.5 months; P = 0.04).
  
  
  CONCLUSIONS
  The RR and TTP were lower than expected and may reflect the reduced dose intensity due to toxicities. While the OS was consistent with previous publications, the efficacy of this combination was not demonstrated.
authors.affiliation: University of Pittsburgh Cancer Institute, PA 15232, USA.
authors.forename: Benedito A
authors.initials: BA
authors.lastname: Carneiro
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ramanathan
authors.forename: Marwan G
authors.initials: MG
authors.lastname: Fakih
authors.forename: Smitha S
authors.initials: SS
authors.lastname: Krishnamurthi
authors.forename: Barry C
authors.initials: BC
authors.lastname: Lembersky
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Stoller
authors.forename: Stewart L
authors.initials: SL
authors.lastname: Lancaster
authors.forename: Richard A
authors.initials: RA
authors.lastname: Pinkerton
authors.forename: Theodore L
authors.initials: TL
authors.lastname: Crandall
authors.forename: Amy R
authors.initials: AR
authors.lastname: Schmotzer
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Potter
authors.forename: Nathan
authors.initials: N
authors.lastname: Bahary
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000077146:Irinotecan; D000068818:Cetuximab; D002166:Camptothecin