Advertisement
Clinical Colorectal Cancer Home
Advanced searchSave search
Research Article| Volume 7, SUPPLEMENT 1, S8-S15, December 2007

Download started.

Ok

A Retrospective on the Inhibition of Epidermal Growth Factor Receptor as a Therapeutic Strategy for Patients with Relapsed Metastatic Colorectal Cancer: Impact on Treatment of Today's Patients

  • Author Footnotes
    1 Dr Jackson has no relevant relationships to disclose.
    Christopher Jackson
    Footnotes
    1 Dr Jackson has no relevant relationships to disclose.
    Affiliations
    Clinical Research Fellow, Royal Marsden Hospital London and Surrey, United Kingdom
    Search for articles by this author
  • Author Footnotes
    2 Dr Cunningham has received research support from Roche, Merck, Amgen, and AstraZeneca and has served as a paid consultant or been on an Advisory Board for Roche, Amgen, Bristol-Myers Squibb, Merck, Pfizer, and AstraZeneca.
    David Cunningham
    Correspondence
    Address for correspondence: David Cunningham MD, FRCP, Gastrointestinal and Lymphoma Units, Royal Marsden Hospital London and Surrey, Downs Rd, Sutton SM2 5PT Surrey, United Kingdom Fax: 44-0-208-643-9414
    Footnotes
    2 Dr Cunningham has received research support from Roche, Merck, Amgen, and AstraZeneca and has served as a paid consultant or been on an Advisory Board for Roche, Amgen, Bristol-Myers Squibb, Merck, Pfizer, and AstraZeneca.
    Affiliations
    Gastrointestinal and Lymphoma Units, Royal Marsden Hospital London and Surrey, United Kingdom
    Search for articles by this author
  • Author Footnotes
    1 Dr Jackson has no relevant relationships to disclose.
    2 Dr Cunningham has received research support from Roche, Merck, Amgen, and AstraZeneca and has served as a paid consultant or been on an Advisory Board for Roche, Amgen, Bristol-Myers Squibb, Merck, Pfizer, and AstraZeneca.
DOI:https://doi.org/10.3816/CCC.2008.s.002
A Retrospective on the Inhibition of Epidermal Growth Factor Receptor as a Therapeutic Strategy for Patients with Relapsed Metastatic Colorectal Cancer: Impact on Treatment of Today's Patients
Previous ArticleTargeting the Right Target: Epidermal Growth Factor Receptor–Directed Individualized Therapy
Next ArticleUpdate on Clinical Data Combining Capecitabine with Targeted Agents in Newly Diagnosed Colorectal Cancer
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      The epidermal growth factor receptor (EGFR) pathway is overexpressed in many colorectal cancers (CRCs) and is associated with a worse prognosis compared with tumors that do not express EGFR. The development of monoclonal antibodies against this receptor, including cetuximab and panitumumab, and small-molecule inhibitors against the tyrosine kinase protein has led to new therapeutic paradigms in the treatment of metastatic CRC (mCRC). The anti-EGFR monoclonal antibody cetuximab has been shown to reverse chemotherapy resistance in patients with irinotecanrefractory mCRC, to improve survival compared with best supportive care (BSC) alone, and to prolong progression free-survival (PFS) in the first-and second-line settings. Panitumumab prolongs PFS compared with BSC, and trials in the first-and second-line settings are ongoing. Clinical trials with tyrosine kinase inhibitors have yielded disappointing results. This article reviews the clinical trial evidence for treatment strategies based on EGFR inhibition in relapsed/refractory mCRC, mechanisms of resistance to EGFR agents, clinical uncertainties, and future directions.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Colorectal Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Register: Create an account
      Institutional Access: Sign in to ScienceDirect

      References

        • Hanahan D
        • Weinberg RA
        The hallmarks of cancer.
        Cell. 2000; 100: 57-70
        • Mendelsohn J
        Targeting the epidermal growth factor receptor for cancer therapy.
        J Clin Oncol. 2002; 20: 1s-13s
        • Goldstein NS
        • Armin M
        Epidermal growth factor receptor immunohistochemical reactivity in patients with American Joint Committee on Cancer Stage IV colon adenocarcinoma: implications for a standardized scoring system.
        Cancer. 2001; 92: 1331-1346
        • Porebska I
        • Harlozinska A
        • Bojarowski T
        Expression of the tyrosine kinase activity growth factor receptors (EGFR, ERB B2, ERB B3) in colorectal adenocarcinomas and adenomas.
        Tumour Biol. 2000; 21: 105-115
        • Spano JP
        • Lagorce C
        • Atlan D
        • et al.
        Impact of EGFR expression on colorectal cancer patient prognosis and survival.
        Ann Oncol. 2005; 16: 102-108
        • Bos M
        • Mendelsohn J
        • Kim YM
        • et al.
        PD153035, a tyrosine kinase inhibitor, prevents epidermal growth factor receptor activation and inhibits growth of cancer cells in a receptor number-dependent manner.
        Clin Cancer Res. 1997; 3: 2099-2106
        • Bruns CJ
        • Harbison MT
        • Davis DW
        • et al.
        Epidermal growth factor receptor blockade with C225 plus gemcitabine results in regression of human pancreatic carcinoma growing orthotopically in nude mice by antiangiogenic mechanisms.
        Clin Cancer Res. 2000; 6: 1936-1948
        • Wu X
        • Fan Z
        • Masui H
        • et al.
        Apoptosis induced by an anti-epidermal growth factor receptor monoclonal antibody in a human colorectal carcinoma cell line and its delay by insulin.
        J Clin Invest. 1995; 95: 1897-1905
        • Masui H
        • Kawamoto T
        • Sato JD
        • et al.
        Growth inhibition of human tumor cells in athymic mice by anti-epidermal growth factor receptor monoclonal antibodies.
        Cancer Res. 1984; 44: 1002-1007
        • Modjtahedi H
        • Eccles S
        • Box G
        • et al.
        Immunotherapy of human tumour xenografts overexpressing the EGF receptor with rat antibodies that block growth factor-receptor interaction.
        Br J Cancer. 1993; 67: 254-261
        • Goldstein NI
        • Prewett M
        • Zuklys K
        • et al.
        Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model.
        Clin Cancer Res. 1995; 1: 1311-1318
        • Yang XD
        • Jia XC
        • Corvalan JR
        • et al.
        Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy.
        Crit Rev Oncol Hematol. 2001; 38: 17-23
        • Saadeh CE
        • Lee HS
        Panitumumab: a fully human monoclonal antibody with activity in metastatic colorectal cancer.
        Ann Pharmacother. 2007; 41: 606-613
        • Kimura H
        • Sakai K
        • Arao T
        • et al.
        Antibody-dependent cellular cytotoxicity of cetuximab against tumor cells with wild-type or mutant epidermal growth factor receptor.
        Cancer Sci. 2007; 98: 1275-1280
        • Kurai J
        • Chikumi H
        • Hashimoto K
        • et al.
        Antibody-dependent cellular cytotoxicity mediated by cetuximab against lung cancer cell lines.
        Clin Cancer Res. 2007; 13: 1552-1561
        • Prewett MC
        • Hooper AT
        • Bassi R
        • et al.
        Enhanced antitumor activity of anti-epidermal growth factor receptor monoclonal antibody IMC-C225 in combination with irinotecan (CPT-11) against human colorectal tumor xenografts.
        Clin Cancer Res. 2002; 8: 994-1003
        • Saltz LB
        • Rubin M
        • Hochster H
        • et al.
        Cetuximab (IMC-C225) plus irinotecan (CPT-11) is active in CPT-11-refractory colorectal cancer (CRC) that expresses epidermal growth factor receptor (EGFR).
        Proc Am Soc Clin Oncol. 2001; 20 (Abstract 7).: 3a
        • Cunningham D
        • Humblet Y
        • Siena S
        • et al.
        Cetuximab monotherapy and cetuxmab plus irinotecan in irinotecan-refractory metastatic colorectal cancer.
        N Eng J Med. 2004; 351: 337-345
        • Souglakos J
        • Kalykaki A
        • Vamvakas L
        • et al.
        Phase II trial of capecitabine and oxaliplatin (CAPOX) plus cetuximab in patients with metastatic colorectal cancer who progressed after oxaliplatin-based chemotherapy.
        Ann Oncol. 2007; 18: 305-310

      20. Sobrero AF, L. Rivera, F. Steinhauer, et al. Randomized phase III trial of cetuximab plus irinotecan versus irinotecan alone for metastatic colorectal cancer in 1298 patients who have failed prior oxaliplatinbased therapy: the EPIC trial. Presented at: the 98th Annual Meeting of the American Association for Cancer Research; April 14-18, 2007; Los Angeles, CA.

        • Tournigand C
        • Andre T
        • Achille E
        • et al.
        FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study.
        J Clin Oncol. 2004; 22: 229-237
        • Saltz LB
        • Lenz H
        • Kindler HL
        • 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.
        J Clin Oncol. 2007; 25: 4516-4518
        • Eng C
        • Maurel J
        • Scheithauer W
        • et al.
        Impact on quality of life of adding cetuximab to irinotecan in patients who have failed prior oxaliplatin-based therapy: the EPIC trial.
        J Clin Oncol. 2007; 25 (Abstract 4003).: 164s
        • Polikoff J
        • Mitchell EP
        • Badarinath S
        • et al.
        Cetuximab plus FOLFOX for colorectal cancer (EXPLORE): preliminary efficacy analysis of a randomized phase III trial.
        J Clin Oncol. 2005; 23 (Abstract 3574).: 264s
      25. US National Institute of Health [Web site].
        Available at: http://wwwclinicaltrials.gov/ct/show/NCT00265850?order=2
        (ClinicalTrials.gov Accessed: September 14, 2007.)
        • Van Cutsem E
        • Peeters M
        • Siena S
        • 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.
        J Clin Oncol. 2007; 25: 1658-1664
        • Jonker DJ
        • O'Callaghan CJ
        • Karapetis CS
        • et al.
        Cetuximab for the treatment of colorectal cancer.
        N Engl J Med. 2007; 357: 2040-2048
        • Saltz LB
        • Meropol NJ
        • Loehrer Sr, PJ
        • et al.
        Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor.
        J Clin Oncol. 2004; 22: 1201-1208
        • Lenz HJ
        • Van Cutsem E
        • Khambata-Ford S
        • et al.
        Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines.
        J Clin Oncol. 2006; 24: 4914-4921
        • Tejpar S
        • Peeters M
        • Humblet Y
        • et al.
        Phase I/II study of cetuximab dose-escalation in patients with metastatic colorectal cancer (mCRC) with no or slight skin reactions on cetuximab standard dose treatment (EVEREST): pharmacokinetic (PK), pharmacodynamic (PD) and efficacy data.
        J Clin Oncol. 2007; 25 (Abstract 4037).: 172s
        • Wood ER
        • Truesdale AT
        • McDonald OB
        • et al.
        A unique structure for epidermal growth factor receptor bound to GW572016 (lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells.
        Cancer Res. 2004; 64: 6652-6659
        • Shepherd FA
        • Rodrigues Pereira J
        • Ciuleanu T
        • et al.
        Erlotinib in previously treated non-small-cell lung cancer.
        N Engl J Med. 2005; 353: 123-132
        • Cohen EE
        • Rosen F
        • Stadler WM
        • et al.
        Phase II trial of ZD1839 in recurrent or metastatic squamous cell carcinoma of the head and neck.
        J Clin Oncol. 2003; 21: 1980-1987
        • Geyer CE
        • Forster J
        • Lindquist D
        • et al.
        Lapatinib plus capecitabine for HER2-positive advanced breast cancer.
        N Engl J Med. 2006; 355: 2733-2743
        • Kindler HL
        • Friberg G
        • Skoog L
        • et al.
        Phase I/II trial of gefitinib and oxaliplatin in patients with advanced colorectal cancer.
        Am J Clin Oncol. 2005; 28: 340-344
        • Vieitez J
        • Valladares M
        • Pelaez I
        • et al.
        A randomised, placebo-controlled, double-blind phase II study of raltitrexed and gefitinib vs raltitrexed alone as 2nd line chemotherapy in subjects with advanced colorectal cancer (CRC). GON group study (Grupo Oncologico del Norte).
        J Clin Oncol. 2007; 25 (Abstract 14523).: 626s
        • Keilholz U
        • Arnold D
        • Niederle N
        • et al.
        Erlotinib as 2nd and 3rd line monotherapy in patients with metastatic colorectal cancer. Results of a multicenter two-cohort phase II trial.
        J Clin Oncol. 2005; 23 (Abstract 3575).: 264s
        • Vincent M
        • Kerr I
        • Dingle B
        • et al.
        Capecitabine (X) compared to X + erlotinib (E) as first-line treatment in patients (pts) with metastatic colorectal cancer (MCRC): interim efficacy results from a randomized phase II study.
        J Clin Oncol. 2007; 25 (Abstract 14560).: 630s
        • Tournigand C
        • Lledo G
        • Delord J
        • et al.
        Modified (m)FOLFOX7/bevacizumab (B) or modified (m)XELOX/bevacizumab with or without erlotinib (E) in first-line metastatic colorectal cancer (mCRC): results of the feasibility phase of the DREAM-OPTIMOX3 study (GERCOR).
        J Clin Oncol. 2007; 25 (Abstract 4097).: 187s
        • Scartozzi M
        • Bearzi I
        • Berardi R
        • et al.
        Epidermal growth factor receptor (EGFR) status in primary colorectal tumors does not correlate with EGFR expression in related metastatic sites: implications for treatment with EGFR-targeted monoclonal antibodies.
        J Clin Oncol. 2004; 22: 4772-4778
        • Finocchiaro G
        • Cappuzzo F
        • Janne PA
        • et al.
        EGFR, HER2 and Kras as predictive factors for cetuximab sensitivity in colorectal cancer.
        J Clin Oncol. 2007; 25 (Abstract 4021).: 168s
        • Lievre A
        • Bachet JB
        • Le Corre D
        • et al.
        KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer.
        Cancer Res. 2006; 66: 3992-3995
        • Di Fiore F
        • Blanchard F
        • Charbonnier F
        • et al.
        Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by cetuximab plus chemotherapy.
        Br J Cancer. 2007; 96: 1166-1169
        • Massarelli E
        • Varella-Garcia M
        • Tang X
        • et al.
        KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer.
        Clin Cancer Res. 2007; 13: 2890-2896
        • Moroni M
        • Veronese S
        • Benvenuti S
        • et al.
        Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study.
        Lancet Oncol. 2005; 6: 279-286
        • Mukohara T
        • Engelman JA
        • Hanna NH
        • et al.
        Differential effects of gefitinib and cetuximab on non-small-cell lung cancers bearing epidermal growth factor receptor mutations.
        J Natl Cancer Inst. 2005; 97: 1185-1194
        • Hecht J
        • Chidiac T
        • Mitchell E
        • et al.
        An interim analysis of efficacy and safety from a randomized controlled trial of panitumumab with chemotherapy plus bevacizumab (Bev) in metastatic colorectal cancer (mCRC).
        Ann Oncol. 2007; 18 (Abstract 0-0033).: vii21
        • Tol J
        • Koopman M
        • Rodenburg CJ
        • et al.
        Randomised phase III study of capecitabine, oxaliplatin and bevacizumab (CAPOXB) with or without cetuximab in advanced colorectal cancer (ACC), the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). An interim safety analysis.
        Eur J Cancer. 2007; 5 (Abstract 3000).: 234
        • Hurwitz H
        • Fehrenbacher L
        • Novotny W
        • et al.
        Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer.
        N Engl J Med. 2004; 350: 2335-2342
        • Van Cutsem E
        • Nowacki M
        • Lang I
        • et al.
        Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the firstline treatment of patients with metastatic colorectal cancer (mCRC): the CRYSTAL trial.
        J Clin Oncol. 2007; 25 (Abstract 4000).: 164s

      Article info

      Publication history

      Accepted: November 26, 2007
      Received in revised form: November 22, 2007
      Received: September 24, 2007

      Footnotes

      This article includes discussion of investigational and/or unlabeled uses of drugs, including the use of gefitinib and erlotinib in relapsed/refractory metastatic colorectal cancer and cetuximab as first-line therapy in metastatic colorectal cancer.

      Identification

      DOI: https://doi.org/10.3816/CCC.2008.s.002

      Copyright

      © 2007 Elsevier Inc. Published by Elsevier Inc. All rights reserved.

      ScienceDirect

      Access this article on ScienceDirect

      The content on this site is intended for healthcare professionals.


      We use cookies to help provide and enhance our service and tailor content. To update your cookie settings, please visit the Cookie Preference Center for this site.
      Copyright © 2023 Elsevier Inc. except certain content provided by third parties.


      RELX