A Randomized Phase II Study of Cetuximab Every 2 Weeks at Either 500 or 750 mg/m2 for Patients With Recurrent or Metastatic Head and Neck Squamous Cell Cancer

Restricted access

Cetuximab is typically administered on a weekly schedule for patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC). This study explores cetuximab administered every 2 weeks (q2w). In this multicenter randomized prospective phase II study, eligible patients (≤2 prior cytotoxic chemotherapy regimens for recurrent or metastatic disease; ECOG performance status ≤2) were randomized to receive cetuximab q2w at 500 mg/m2 (Group A) or 750 mg/m2 (Group B). The primary end point was response rate (RECIST 1.0). Sixty-one patients were enrolled: 35 in Group A and 26 in Group B, which was closed early for lack of efficacy. Confirmed partial response rates were 11% for Group A (4/35) and 8% for Group B (2/26) according to intention to treat analysis. Partial responses occurred only among patients whose primary tumors were in the oral cavity or larynx. Median progression-free survival (PFS) and median overall survival (OS) were similar for both groups (PFS, 2.2 and 2.0 months; OS, 7.0 and 9.4 months; Groups A and B, respectively). The most common cetuximab-related adverse events (all grades) among treated subjects included rash, fatigue, and hypomagnesemia. Cetuximab, 500 mg/m2, q2w achieves similar efficacy as conventional dosing for patients with recurrent or metastatic HNSCC. Escalating the dose to 750 mg/m2 q2w offers no obvious therapeutic advantage.

Correspondence: Matthew G. Fury, MD, PhD, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Department of Medicine, Box 532, New York, NY 10021. E-mail: JNCCN@nccn.org
  • 1

    AngKKBerkeyBATuX. Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res2002;62:73507356.

    • Search Google Scholar
    • Export Citation
  • 2

    Rubin GrandisJMelhemMFGoodingWE. Levels of TGF-alpha and EGFR protein in head and neck squamous cell carcinoma and patient survival. J Natl Cancer Inst1998;90:824832.

    • Search Google Scholar
    • Export Citation
  • 3

    SharafinskiMEFerrisRLFerroneSGrandisJR. Epidermal growth factor receptor targeted therapy of squamous cell carcinoma of the head and neck. Head Neck2010;32:14121421.

    • Search Google Scholar
    • Export Citation
  • 4

    LiSSchmitzKRJeffreyPD. Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell2005;7:301311.

    • Search Google Scholar
    • Export Citation
  • 5

    SpecenierPVermorkenJB. Cetuximab in the treatment of squamous cell carcinoma of the head and neck. Expert Rev Anticancer Ther2011;11:511524.

    • Search Google Scholar
    • Export Citation
  • 6

    BaselgaJTrigoJMBourhisJ. Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol2005;23:55685577.

    • Search Google Scholar
    • Export Citation
  • 7

    VermorkenJBTrigoJHittR. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based chemotherapy. J Clin Oncol2007;25:21712177.

    • Search Google Scholar
    • Export Citation
  • 8

    BurtnessBGoldwasserMAFloodW. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer. J Clin Oncol2005;23:86468654.

    • Search Google Scholar
    • Export Citation
  • 9

    VermorkenJBMesiaRRiveraF. Platinum-based chemotherapy plus cetuximab in head and neck cancer. New Engl J Med2008;359:11161127.

  • 10

    BaselgaJPfisterDCooperMR. Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. J Clin Oncol2000;18:904914.

    • Search Google Scholar
    • Export Citation
  • 11

    ShinDMDonatoNJPerez-SolerR. Epidermal growth factor receptor-targeted therapy with C225 and cisplatin in patients with head and neck cancer. Clin Cancer Res2001;7:12041213.

    • Search Google Scholar
    • Export Citation
  • 12

    TaberneroJCiardielloFRiveraF. Cetuximab administered once every second week to patients with metastatic colorectal cancer: a two-part pharmacokinetic/pharmacodynamic phase I dose escalation cetuximab. Ann Oncol2010;21:15371545.

    • Search Google Scholar
    • Export Citation
  • 13

    TaberneroJPfeifferPCervantesA. Administration of cetuximab every 2 weeks in the treatment of metastatic colorectal cancer: an effective, more convenient alternative to weekly administration?Oncologist2008;13:113119.

    • Search Google Scholar
    • Export Citation
  • 14

    TaberneroJCervantesARiveraF. Pharmacogenomic and pharmacogenetic studies of cetuximab in metastatic colorectal cancer: biomarker analysis of phase I dose escalation study. J Clin Oncol2010;28:11811189.

    • Search Google Scholar
    • Export Citation
  • 15

    Martin-MartorelliPRoselloSRodriguez-BraunE. Biweekly cetuximab and irinotecan in advanced colorectal cancer patients progressing after at least one previous line of chemotherapy: results of a phase II single institution trial. Br J Cancer2008;99:455458.

    • Search Google Scholar
    • Export Citation
  • 16

    PfeifferPNielsenDBjerregaardJ. Biweekly cetuximab and irinotecan as third line therapy in patients with advanced colorectal cancer after failure of irinotecan, oxaliplatin, and 5-fluorouracil. Ann Oncol2008;19:11411145.

    • Search Google Scholar
    • Export Citation
  • 17

    TherassePArbuckSGEisenhauerEA. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst2000;92:205216.

    • Search Google Scholar
    • Export Citation
  • 18

    CohenEE. Role of epidermal growth factor receptor pathway-targeted therapy in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. J Clin Oncol2006;24:26592665.

    • Search Google Scholar
    • Export Citation
  • 19

    BouchahdaMMacarullaTLiedoG. Feasibility of cetuximab given wtih a simplified schedule every 2 weeks in advanced colorectal cancer: a multicenter, retrospective analysis. Med Oncol2011;28(Suppl 1):S253258.

    • Search Google Scholar
    • Export Citation
  • 20

    VidalLGillisonML. Human papillomavirus in HNSCC: recognition of a distinct disease type. Hematol Oncol Clin N Am2008;22:11251142.

  • 21

    SchoennemannKRBjerregaardJKHansenTP. Biweeky cetuximab and irinotecan as second line therapy in patients with gastro-esophageal cancer previously treated with platinum. Gastric Cancer2011;14:219225.

    • Search Google Scholar
    • Export Citation
  • 22

    PfeifferPNielsenDBjerregaardJ. Biweekly cetuximab and irinotecan as third line therapy in patients with advanced colorectal cancer after failure to irinotecan, oxaliplatin, and 5-fluorouracil. Ann Oncol2008;19:11411145.

    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 194 194 20
PDF Downloads 82 82 15
EPUB Downloads 0 0 0