title: Phase II study of FOLFOX, bevacizumab and erlotinib as first-line therapy for patients with metastatic colorectal cancer.
abstract: BACKGROUND
  Targeting the epidermal growth factor receptor and angiogenesis have proven useful strategies against metastatic colorectal cancer. The benefit of combining inhibitors of both pathways is unknown.
  
  
  METHODS
  Patients with previously untreated metastatic colorectal cancer were enrolled in a phase II trial of infusional 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX), bevacizumab and erlotinib. The primary end point was progression-free survival.
  
  
  RESULTS
  Thirty-five patients were enrolled and all came off trial for reasons other than progression; 18 (51%) had protocol-defined adverse events requiring removal, nine (26%) withdrew consent due to toxicity, six pursued surgery or localized therapies and two requested a treatment holiday. Principal toxic effects included rash, neuropathy and diarrhea. Seven patients came off trial before first restaging. By intention-to-treat analysis, one patient had a confirmed complete response, 10 had confirmed partial responses and one had an unconfirmed partial response (response rate = 34%). One patient had progressive disease at time of withdrawal from the trial, thus progression-free survival could not be calculated.
  
  
  CONCLUSIONS
  The combination of FOLFOX, bevacizumab and erlotinib led to higher than expected early withdrawal due to toxicity, limiting conclusions regarding efficacy. These findings raise concern regarding the tolerability of adding more agents to already complex combination regimens for metastatic colorectal cancer.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. jmeyerhardt@partners.org
authors.forename: J A
authors.initials: JA
authors.lastname: Meyerhardt
authors.forename: K
authors.initials: K
authors.lastname: Stuart
authors.forename: C S
authors.initials: CS
authors.lastname: Fuchs
authors.forename: A X
authors.initials: AX
authors.lastname: Zhu
authors.forename: C C
authors.initials: CC
authors.lastname: Earle
authors.forename: P
authors.initials: P
authors.lastname: Bhargava
authors.forename: L
authors.initials: L
authors.lastname: Blaszkowsky
authors.forename: P
authors.initials: P
authors.lastname: Enzinger
authors.forename: R J
authors.initials: RJ
authors.lastname: Mayer
authors.forename: S
authors.initials: S
authors.lastname: Battu
authors.forename: C
authors.initials: C
authors.lastname: Lawrence
authors.forename: D P
authors.initials: DP
authors.lastname: Ryan
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000069347:Erlotinib Hydrochloride; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D011799:Quinazolines; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride; D002955:Leucovorin; D005472:Fluorouracil