title: Panitumumab with irinotecan/leucovorin/5-fluorouracil for first-line treatment of metastatic colorectal cancer.
abstract: OBJECTIVE
  Panitumumab is a fully human monoclonal antibody directed against the epidermal growth factor receptor and is indicated for patients with metastatic colorectal cancer (mCRC) who have experienced disease progression after standard chemotherapy. We conducted this phase II study to assess the ability of panitumumab to be administered with first-line irinotecan-containing regimens in patients with mCRC.
  
  
  METHODS
  This was a 2-part multicenter study of panitumumab 2.5 mg/kg weekly with irinotecan, 5-fluorouracil (5-FU), and leucovorin. Part 1 used bolus 5-FU (IFL), and part 2 used infusional 5-FU (FOLFIRI). Tolerability (measured by grade 3/4 diarrhea) was the primary endpoint. Objective response, progression-free survival, overall survival, and safety were also examined.
  
  
  RESULTS
  Nineteen patients in part 1 and 24 patients in part 2 received panitumumab plus chemotherapy. Grade 3/4 diarrhea occurred in 11 patients (58%) in part 1 and 6 patients (25%) in part 2. All patients had a skin-related toxicity (no grade 4 events). Objective response rates were 46% in part 1 and 42% in part 2. Disease control rates were 74% in part 1 and 79% in part 2. Median progression-free survival (95% confidence interval) was 5.6 months (4.4-8.3 months) for part 1 and 10.9 months (7.7-22.5 months) for part 2. Median overall survival (95% confidence interval) was 17 months (13.7 months to not estimable) for part 1 and 22.5 months (14.4 months to not estimable) for part 2.
  
  
  CONCLUSIONS
  In patients with mCRC, panitumumab/IFL was not well tolerated. Panitumumab/FOLFIRI was well tolerated, showed promising activity, and is undergoing further investigation.
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN 37232-6307, USA. jordan.berlin@vanderbilt.edu
authors.forename: Jordan
authors.initials: J
authors.lastname: Berlin
authors.forename: James
authors.initials: J
authors.lastname: Posey
authors.forename: Simon
authors.initials: S
authors.lastname: Tchekmedyian
authors.forename: Eddie
authors.initials: E
authors.lastname: Hu
authors.forename: David
authors.initials: D
authors.lastname: Chan
authors.forename: Imtiaz
authors.initials: I
authors.lastname: Malik
authors.forename: Liqiang
authors.initials: L
authors.lastname: Yang
authors.forename: Rafael G
authors.initials: RG
authors.lastname: Amado
authors.forename: J Randolph
authors.initials: JR
authors.lastname: Hecht
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000077544:Panitumumab; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000911:Antibodies, Monoclonal; D014803:Vitamin B Complex; D000077544:Panitumumab; D000077146:Irinotecan; D066246:ErbB Receptors; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin