title: A phase II study of capecitabine, oxaliplatin, and cetuximab with or without bevacizumab as frontline therapy for metastatic colorectal cancer. A Fox Chase extramural research study.
abstract: OBJECTIVE
  Dual inhibition of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) demonstrated initial promise in clinical trials. This phase II study tested the efficacy and safety of capecitabine, oxaliplatin, and cetuximab with or without bevacizumab as first-line treatment for metastatic colorectal cancer patients.
  
  
  METHODS
  Patients were randomized to receive capecitabine 850 mg/m2 PO twice daily for 14 days, oxaliplatin 130 mg/ m2 IV day 1, and cetuximab 400 mg/m2 IV loading dose followed by 250 mg/m2 IV days 1, 8, and 15 with (arm A) or without (Arm B) bevacizumab 7.5 mg/kg IV day 1 every 21 days. Tumor samples were collected and retrospectively analyzed for KRAS mutation status. The primary endpoint was response rate, with time to progression (TTP) and overall survival (OS) as secondary objectives.
  
  
  RESULTS
  Twenty-three patients (12 in arm A, 11 in arm B) were enrolled onto the study. Median follow-up was 25.9 months. Both treatments were well tolerated, with expected higher rates of grade 1/2 hypertension and bleeding in arm A. The overall response rate was 54% (36.4% in arm A and 72.7% in arm B). Median time to progression was 8.7 months in arm A and 14.4 months in arm B. The median survival was 18.0 months in arm A and 42.5 months in arm B. The study was prematurely terminated after other studies reported inferior outcomes with dual antibody therapy.
  
  
  CONCLUSIONS
  Although terminated early, the study supports the detrimental effect of combining VEGF and EGFR inhibition in metastatic colorectal cancer.
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA. efrat.dotan@fccc.edu
authors.forename: Efrat
authors.initials: E
authors.lastname: Dotan
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Meropol
authors.forename: Barbara
authors.initials: B
authors.lastname: Burtness
authors.forename: Crystal S
authors.initials: CS
authors.lastname: Denlinger
authors.forename: James
authors.initials: J
authors.lastname: Lee
authors.forename: David
authors.initials: D
authors.lastname: Mintzer
authors.forename: Fang
authors.initials: F
authors.lastname: Zhu
authors.forename: Karen
authors.initials: K
authors.lastname: Ruth
authors.forename: Holly
authors.initials: H
authors.lastname: Tuttle
authors.forename: Judi
authors.initials: J
authors.lastname: Sylvester
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Cohen
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D000069287:Capecitabine; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D000068818:Cetuximab; D005472:Fluorouracil