title: A phase I study of cetuximab/paclitaxel in patients with advanced-stage breast cancer.
abstract: BACKGROUND
  The epidermal growth factor receptor (EGFR) is part of the ErbB family of receptor tyrosine kinases and is known to be variably expressed in breast cancers. Cetuximab is a humanized monoclonal antibody directed against the EGFR that works by blocking the downstream signaling function of this protein and thereby interfering with cancer cell proliferation. Preclinical studies have indicated a synergistic effect for the combination of anti-EGFR therapy plus paclitaxel in breast cancer models.
  
  
  METHODS
  Hence, we conducted a dose-escalation phase I trial using cetuximab/paclitaxel in patients with metastatic breast cancer to evaluate the feasibility of this combination. Patients with EGFR-positive metastatic breast cancer treated with <or= 1 previous therapy, excluding taxanes, were eligible. Treatment consisted of weekly cetuximab therapy and every-3-week paclitaxel, with dose escalation of cetuximab until the maximum tolerated dose was reached.
  
  
  RESULTS
  Twelve patients were enrolled to 3 treatment cohorts. Two of 6 patients on the second cohort (cetuximab 100 mg/m2) developed dose-limiting toxicities, presenting as grade 3 rash. The third cohort was amended to allow the same cetuximab dose but to modify the paclitaxel to a weekly schedule. Despite this, 1 of 3 patients in this group also developed grade 3 skin toxicity as a dose-limiting toxicity; thus, the trial was stopped. Ten of the 12 patients were evaluable for response, and of these, 2 patients experienced stable disease, and 8 patients experienced disease progression.
  
  
  CONCLUSIONS
  Because of prohibitive dermatologic toxicity and disappointing preliminary efficacy, the combination of paclitaxel/cetuximab was not considered promising in this population, although further study of this regimen might be warranted.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Shanu
authors.initials: S
authors.lastname: Modi
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Andrea
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: Tzy Jyun
authors.initials: TJ
authors.lastname: Yao
authors.forename: James
authors.initials: J
authors.lastname: Caravelli
authors.forename: Peter P
authors.initials: PP
authors.lastname: Rosen
authors.forename: Clifford
authors.initials: C
authors.lastname: Hudis
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Seidman
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000068818:Cetuximab; D004357:Drug Synergism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab; D066246:ErbB Receptors; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases