Targeting colorectal cancer with human anti-EGFR monoclonocal antibodies: focus on panitumumab

The human anti-epidermal growth factor receptor (EGFR) monoclonal antibody, panitumumab, represents a significant advance in the treatment of colorectal cancer. The strategy to target this receptor is based on sound cancer biology demonstrating its essential role in colorectal carcinogenesis. Panitumumab, unlike its predecessor, cetuximab, is fully human and thus reduces the incidence of hypersensitivity reactions. But, in several clinical trials, unexpected toxicities have become more apparent, raising concerns of how readily panitumumab can succeed cetuximab. This paper reviews the development of this agent and the pivotal clinical trials that help our understanding of its optimal use in colorectal cancer treatment.

[1]  Neal J Meropol,et al.  Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  R. Figlin,et al.  Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody. , 2004, International journal of radiation oncology, biology, physics.

[3]  E. Van Cutsem,et al.  Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  R. Mayer,et al.  Analysis of EGFR status in metastatic colorectal cancer patients treated with cetuximab monotherapy , 2005 .

[5]  B. Vogelstein,et al.  A genetic model for colorectal tumorigenesis , 1990, Cell.

[6]  C. Köhne,et al.  Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): The CRYSTAL trial , 2007 .

[7]  R. Figlin,et al.  Updated results from a dose and schedule study of Panitumumab (ABX-EGF) monotherapy, in patients with advanced solid malignancies , 2005 .

[8]  J. Berlin,et al.  Safety and efficacy of panitumumab monotherapy in patients with metastatic colorectal cancer (mCRC) , 2005 .

[9]  John Mendelsohn,et al.  Type I Receptor Tyrosine Kinases as Targets for Therapy in Breast Cancer , 2004, Journal of Mammary Gland Biology and Neoplasia.

[10]  A. Citri,et al.  EGF–ERBB signalling: towards the systems level , 2006, Nature Reviews Molecular Cell Biology.

[11]  Daniel J. Freeman,et al.  Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  J. Berlin,et al.  High incidence of cetuximab-related infusion reactions in Tennessee and North Carolina and the association with atopic history. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  J. Berlin,et al.  Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer , 2007, Cancer.

[14]  R. Janknegt An interim analysis , 1990 .

[15]  L. Schwartz,et al.  Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  Dongsheng Tu,et al.  Cetuximab for the treatment of colorectal cancer. , 2007, The New England journal of medicine.

[17]  J. Baselga,et al.  Targeting the epidermal growth factor receptor: a clinical reality. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  J. L. Bos,et al.  ras oncogenes in human cancer: a review. , 1989, Cancer research.

[19]  M. Gonen,et al.  Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: the BOND-2 study. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  J. Mendelsohn Targeting the epidermal growth factor receptor for cancer therapy. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  C. Davis,et al.  Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. , 2001, Critical reviews in oncology/hematology.

[22]  N. Dubrawsky Cancer statistics , 1989, CA: a cancer journal for clinicians.

[23]  J. Gamero Treatment of colorectal cancer. , 1976, JAMA.

[24]  A. Jemal,et al.  Cancer Statistics, 2008 , 2008, CA: a cancer journal for clinicians.

[25]  J. Berlin,et al.  Panitumumab with irinotecan/leucovorin/5-fluorouracil for first-line treatment of metastatic colorectal cancer. , 2007, Clinical colorectal cancer.

[26]  Armando Santoro,et al.  Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. , 2004, The New England journal of medicine.

[27]  Richard L Schilsky,et al.  Cetuximab in the treatment of colorectal cancer. , 2004, Clinical advances in hematology & oncology : H&O.

[28]  Y. Nishimura,et al.  AN INTERIM ANALYSIS , 2005 .

[29]  Marc Peeters,et al.  Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  K. Kinzler,et al.  Somatic mutations of EGFR in colorectal cancers and glioblastomas. , 2004, The New England journal of medicine.

[31]  W. Scheithauer,et al.  EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[32]  J. Hecht,et al.  Panitumumab activity in metastatic colorectal cancer (mCRC) patients (pts) with low or negative tumor epidermal growth factor receptor (EGFr) levels: An updated analysis , 2007 .