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Research Article| Volume 7, SUPPLEMENT 1, S28-S36, December 2007

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Exploring Alternative Individualized Treatment Strategies in Colorectal Cancer

  • Author Footnotes
    1 Dr Wilson has no relevant relationships to disclose.
    Peter M. Wilson
    Footnotes
    1 Dr Wilson has no relevant relationships to disclose.
    Affiliations
    Department of Pathology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles
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  • Author Footnotes
    2 Dr Ladner has no relevant relationships to disclose.
    Robert D. Ladner
    Footnotes
    2 Dr Ladner has no relevant relationships to disclose.
    Affiliations
    Department of Pathology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles
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  • Author Footnotes
    3 Dr Lenz has received research support from Roche, Bristol-Myers Squibb, Eli Lilly, sanofi-aventis, Novartis Oncology, Genentech BioOncology, ImClone, Pfizer, and AstraZeneca, has served as a paid consultant or been on an Advisory Board for Merck, Response Genetics, Genentech BioOncology, Amgen, Novartis Oncology, sanofi-aventis, Pfizer, Bristol-Myers Squibb, and ImClone, and has served on a Speaker's Bureau for Roche, Pfizer, Eli Lilly, sanofi-aventis, and Merck.
    Heinz-Josef Lenz
    Correspondence
    Address for correspondence: Heinz-Josef Lenz, MD, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, 1441 Eastlake Ave, Suite 3456, Los Angeles, CA 90033 Fax: 323-865-0061
    Footnotes
    3 Dr Lenz has received research support from Roche, Bristol-Myers Squibb, Eli Lilly, sanofi-aventis, Novartis Oncology, Genentech BioOncology, ImClone, Pfizer, and AstraZeneca, has served as a paid consultant or been on an Advisory Board for Merck, Response Genetics, Genentech BioOncology, Amgen, Novartis Oncology, sanofi-aventis, Pfizer, Bristol-Myers Squibb, and ImClone, and has served on a Speaker's Bureau for Roche, Pfizer, Eli Lilly, sanofi-aventis, and Merck.
    Affiliations
    Division of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles
    Search for articles by this author
  • Author Footnotes
    1 Dr Wilson has no relevant relationships to disclose.
    2 Dr Ladner has no relevant relationships to disclose.
    3 Dr Lenz has received research support from Roche, Bristol-Myers Squibb, Eli Lilly, sanofi-aventis, Novartis Oncology, Genentech BioOncology, ImClone, Pfizer, and AstraZeneca, has served as a paid consultant or been on an Advisory Board for Merck, Response Genetics, Genentech BioOncology, Amgen, Novartis Oncology, sanofi-aventis, Pfizer, Bristol-Myers Squibb, and ImClone, and has served on a Speaker's Bureau for Roche, Pfizer, Eli Lilly, sanofi-aventis, and Merck.
DOI:https://doi.org/10.3816/CCC.2008.s.005
Exploring Alternative Individualized Treatment Strategies in Colorectal Cancer
Previous ArticleUpdate on Clinical Data with Regimens Inhibiting Angiogenesis and Epidermal Growth Factor Receptor for Patients with Newly Diagnosed Metastatic Colorectal Cancer
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      Abstract

      Colorectal cancer (CRC) is the third most commonly diagnosed cancer in men and women in the United States, with a predicted 154,000 new cases this year. For > 40 years, 5-fluorouracil (5-FU) has remained the central agent in therapeutic regimens used in the treatment of CRC, with single-agent response rates (RRs) of 20%-25% in advancedstage disease. The past decade has witnessed the introduction of newer agents, such as the DNA-damaging agents oxaliplatin and irinotecan, which when used in combination with 5-FU, have dramatically increased RRs to 40%-50% in advanced disease and improved overall survival. The development of monoclonal antibodies targeting the epidermal growth factor receptor or vascular endothelial growth factor have now demonstrated additional clinical benefit for patients with metastatic disease, and the clinical development of these agents continues to progress. However, many patients will die, and a significant proportion will experience severe chemotherapy-induced toxicities, while deriving little or no benefit. Global efforts are currently under way to identify reliable and validated cassettes of markers with the ability to predict response and toxicity from a chemotherapeutic regimen. In addition, the ability to accurately predict patients with early-stage disease at high risk of recurrence will enable the appropriate administration of adjuvant therapy. The emerging cancer stem cell hypothesis continues to gain momentum with ongoing research, suggesting this might become one of the prime targets for future therapy. Together, these approaches are spearheading a paradigm shift toward individualized treatment strategies in CRC treatment.

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      References

      1. American Cancer Society [Web site]. Estimated new cancer cases and deaths by sex for all sites, US, 2007.
        Available at: http://www.cancer.org/downloads/STT/CAFF2007leadingsites.pdf
        (Accessed: November 20, 2006.)
        • Douillard JY
        • Cunningham D
        • Roth AD
        • et al.
        Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial.
        Lancet. 2000; 355: 1041-1047
        • Giacchetti S
        • Perpoint B
        • Zidani R
        • et al.
        Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracilleucovorin as first-line treatment of metastatic colorectal cancer.
        J Clin Oncol. 2000; 18: 136-147
        • Tournigand C
        • André 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
        • Hoff PM
        • Ansari R
        • Batist G
        • et al.
        Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study.
        J Clin Oncol. 2001; 19: 2282-2292
        • Van Cutsem E
        • Twelves C
        • Cassidy J
        • et al.
        Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study.
        J Clin Oncol. 2001; 19: 4097-4106
        • Cunningham D
        • Humblet Y
        • Siena S
        • et al.
        Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer.
        N Engl J Med. 2004; 351: 337-345
        • McLeod HL
        • Yu J
        Cancer pharmacogenomics: SNPs, chips, and the individual patient.
        Cancer Invest. 2003; 21: 630-640
        • Longley DB
        • Allen WL
        • Johnston PG
        Drug resistance, predictive markers and pharmacogenomics in colorectal cancer.
        Biochim Biophys Acta. 2006; 1766: 184-196
        • Greene FL
        • Stewart AK
        • Norton HJ
        A new TNM staging strategy for node-positive (stage III) colon cancer: an analysis of 50,042 patients.
        Ann Surg. 2002; 236 (discussion 421.): 416-421
        • Meyerhardt JA
        • Mayer RJ
        Systemic therapy for colorectal cancer.
        N Engl J Med. 2005; 352: 476-487
        • O'Connell JB
        • Maggard MA
        • Ko CY
        Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging.
        J Natl Cancer Inst. 2004; 96: 1420-1425
        • Longley DB
        • Harkin DP
        • Johnston PG
        5-fluorouracil: mechanisms of action and clinical strategies.
        Nat Rev Cancer. 2003; 3: 330-338
        • Twelves C
        • Wong A
        • Nowacki MP
        • et al.
        Capecitabine as adjuvant treatment for stage III colon cancer.
        N Engl J Med. 2005; 352: 2696-2704
        • André T
        • Boni C
        • Mounedji-Boudiaf L
        • et al.
        Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer.
        N Engl J Med. 2004; 350: 2343-2351
        • Saltz LB
        • Niedzwiecki D
        • Hollis D
        • et al.
        Irinotecan fluorouracil plus leucovorin is not superior to fluorouracil plus leucovorin alone as adjuvant treatment for stage III colon cancer: results of CALGB 89803.
        J Clin Oncol. 2007; 25: 3456-3461
        • Gray RG
        • Barnwell J
        • Hills R
        QUASAR: a randomized study of adjuvant chemotherapy vs. observation in 3238 colorectal cancer patients.
        Proc Am Soc Clin Oncol. 2004; 22 (Abstract 3501).: 246
        • Gill S
        • Loprinzi CL
        • Sargent DJ
        • et al.
        Pooled analysis of fluorouracilbased adjuvant therapy for stage II and III colon cancer: who benefits and by how much?.
        J Clin Oncol. 2004; 22: 1797-1806
        • Benson III, AB
        • Schrag D
        • Somerfield MR
        • et al.
        American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer.
        J Clin Oncol. 2004; 22: 3408-3419
        • Piñol V
        • Castells A
        • Andreu M
        • et al.
        Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer.
        JAMA. 2005; 293: 1986-1994
        • Gryfe R
        • Gallinger S
        Microsatellite instability, mismatch repair deficiency, and colorectal cancer.
        Surgery. 2001; 130: 17-20
        • Lim SB
        • Jeong SY
        • Lee MR
        • et al.
        Prognostic significance of microsatellite instability in sporadic colorectal cancer.
        Int J Colorectal Dis. 2004; 19: 533-537
        • Popat S
        • Hubner R
        • Houlston RS
        Systematic review of microsatellite instability and colorectal cancer prognosis.
        J Clin Oncol. 2005; 23: 609-618
        • Watanabe T
        • Wu TT
        • Catalano PJ
        • et al.
        Molecular predictors of survival after adjuvant chemotherapy for colon cancer.
        N Engl J Med. 2001; 344: 1196-1206
        • Fallik D
        • Borrini F
        • Boige V
        • et al.
        Microsatellite instability is a predictive factor of the tumor response to irinotecan in patients with advanced colorectal cancer.
        Cancer Res. 2003; 63: 5738-5744
        • Kern SE
        • Fearon ER
        • Tersmette KW
        • et al.
        Clinical and pathological associations with allelic loss in colorectal carcinoma [corrected].
        JAMA. 1989; 261: 3099-3103
        • Khine K
        • Smith DR
        • Goh HS
        High frequency of allelic deletion on chromosome 17p in advanced colorectal cancer.
        Cancer. 1994; 73: 28-35
        • Lanza G
        • Matteuzzi M
        • Gafá R
        • et al.
        Chromosome 18q allelic loss and prognosis in stage II and III colon cancer.
        Int J Cancer. 1998; 79: 390-395
        • Popat S
        • Houlston RS
        A systematic review and meta-analysis of the relationship between chromosome 18q genotype, DCC status and colorectal cancer prognosis.
        Eur J Cancer. 2005; 41: 2060-2070
      30. (ClinicalTrials.gov)
        [Web site]. Oxaliplatin, leucovorin, and fluorouracil with or without bevacizumab in treating patients who have undergone surgery for stage II colon cancer.
        Available at: http://www.clinicaltrials.gov/ct/gui/show/NCT00217737
        (Accessed: November 20, 2006.)
        • Lurje G
        • Schultheis AM
        • Hendifar AE
        • et al.
        VEGF and VEGF receptor-2 (VEGFR2) gene polymorphisms predict tumor recurrence in stage II and III colon cancer.
        J Clin Oncol. 2007; 25 (Abstract 4004).: 164s
        • Wang Y
        • Jatkoe T
        • Zhang Y
        • et al.
        Gene expression profiles and molecular markers to predict recurrence of Dukes' B colon cancer.
        J Clin Oncol. 2004; 22: 1564-1571
        • Herbst RS
        • Langer CJ
        Epidermal growth factor receptors as a target for cancer treatment: the emerging role of IMC-C225 in the treatment of lung and head and neck cancers.
        Semin Oncol. 2002; 29: 27-36
        • Wilson PM
        • Ladner RJ
        • Lenz HJ
        Predictive and prognostic makers in colorectal cancer.
        Gastrointest Cancer Res. 2007; (In press.)
        • Ciardiello F
        Epidermal growth factor receptor tyrosine kinase inhibitors as anticancer agents.
        Drugs. 2000; 60 (discussion 41-2.): 25-32
        • McKay JA
        • Murray LJ
        • Curran S
        • et al.
        Evaluation of the epidermal growth factor receptor (EGFR) in colorectal tumours and lymph node metastases.
        Eur J Cancer. 2002; 38: 2258-2264
        • Resnick MB
        • Routhier J
        • Konkin T
        • et al.
        Epidermal growth factor receptor, c-MET, beta-catenin, and p53 expression as prognostic indicators in stage II colon cancer: a tissue microarray study.
        Clin Cancer Res. 2004; 10: 3069-3075
        • Gibson TB
        • Ranganathan A
        • Grothey A
        Randomized phase III trial results of panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, in metastatic colorectal cancer.
        Clin Colorectal Cancer. 2006; 6: 29-31
        • Mendelsohn J
        • Baselga J
        The EGF receptor family as targets for cancer therapy.
        Oncogene. 2000; 19: 6550-6565
        • Lièvre 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
        • De Roock W
        • De Schutter J
        • De Hertogh G
        • et al.
        KRAS mutations preclude tumor shrinkage of colorectal cancers treated with cetuximab.
        J Clin Oncol. 2007; 25 (Abstract 4132).: 196s

      42. Romagnani E, Martin V, Ghisletta M, et al. EGFR gene status, K-Ras mutation and PTEN expression predict cetuximab response in metastatic colorectal cancer (mCRC). Presented at: the 2007 Gastrointestinal Cancers Symposium; January 19-21, 2007; Orlando, FL. Abstract 427.

        • Khambata-Ford S
        • Garrett CR
        • Meropol NJ
        • et al.
        Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab.
        J Clin Oncol. 2007; 25: 3230-3237

      44. Amado RG, Wolf M, Freeman D, et al. KRAS Mutation predicts lack of response to EGFR inhibitors. Presented at: 14th European Cancer Conference; September 27, 2007; Barcelona, Spain. Abstracts 7LB and 3014.

        • Ferrara N
        • Davis-Smyth T
        The biology of vascular endothelial growth factor.
        Endocr Rev. 1997; 18: 4-25
        • Cascinu S
        • Graziano F
        • Catalano V
        • et al.
        An analysis of p53, BAX and vascular endothelial growth factor expression in node-positive rectal cancer. Relationships with tumour recurrence and event-free survival of patients treated with adjuvant chemoradiation.
        Br J Cancer. 2002; 86: 744-749
        • Lee JC
        • Chow NH
        • Wang ST
        • et al.
        Prognostic value of vascular endothelial growth factor expression in colorectal cancer patients.
        Eur J Cancer. 2000; 36: 748-753
        • Nakayama Y
        • Sako T
        • Shibao K
        • et al.
        Prognostic value of plasma vascular endothelial growth factor in patients with colorectal cancer.
        Anticancer Res. 2002; 22: 2437-2442
        • Kim KJ
        • Li B
        • Winer J
        • et al.
        Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo.
        Nature. 1993; 362: 841-844
        • Cascinu S
        • Staccioli MP
        • Gasparini G
        • et al.
        Expression of vascular endothelial growth factor can predict event-free survival in stage II colon cancer.
        Clin Cancer Res. 2000; 6: 2803-2807
        • Ishigami SI
        • Arii S
        • Furutani M
        • et al.
        Predictive value of vascular endothelial growth factor (VEGF) in metastasis and prognosis of human colorectal cancer.
        Br J Cancer. 1998; 78: 1379-1384
        • 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
        • Mass RD
        • Fyfe G
        • Hambleton J
        • et al.
        Bevacizumab in combination with 5-FU/leucovorin improves survival in patients with metastatic colorectal cancer: a combined analysis.
        Proc Am Soc Clin Oncol. 2004; 23 (Abstract 3616).: 274
        • Watnick RS
        • Cheng YN
        • Rangarajan A
        • et al.
        Ras modulates Myc activity to repress thrombospondin-1 expression and increase tumor angiogenesis.
        Cancer Cell. 2003; 3: 219-231
        • Yu JL
        • Rak JW
        • Coomber BL
        • et al.
        Effect of p53 status on tumor response to antiangiogenic therapy.
        Science. 2002; 295: 1526-1528
        • Ince WL
        • Jubb AM
        • Holden SN
        • et al.
        Association of k-ras, b-raf, and p53 status with the treatment effect of bevacizumab.
        J Natl Cancer Inst. 2005; 97: 981-989
        • Jubb AM
        • Hurwitz HI
        • Bai W
        • et al.
        Impact of vascular endothelial growth factor-A expression, thrombospondin-2 expression, and microvessel density on the treatment effect of bevacizumab in metastatic colorectal cancer.
        J Clin Oncol. 2006; 24: 217-227
        • Huang S
        • Mills L
        • Mian B
        • et al.
        Fully humanized neutralizing antibodies to interleukin-8 (ABX-IL8) inhibit angiogenesis, tumor growth, and metastasis of human melanoma.
        Am J Pathol. 2002; 161: 125-134
        • Clarke MF
        • Becker MW
        Stem cells: the real culprits in cancer?.
        Sci Am. 2006; 295: 52-59
        • O'Brien CA
        • Pollett A
        • Gallinger S
        • et al.
        A human colon cancer cell capable of initiating tumour growth in immunodeficient mice.
        Nature. 2007; 445: 106-110
        • Ricci-Vitiani L
        • Lombardi DG
        • Pilozzi E
        • et al.
        Identification and expansion of human colon-cancer-initiating cells.
        Nature. 2007; 445: 111-115
        • Cashen AF
        • Nervi B
        • DiPersio J
        AMD3100: CXCR4 antagonist and rapid stem cell-mobilizing agent.
        Future Oncol. 2007; 3: 19-27
        • Meijer L
        • Flajolet M
        • Greengard P
        Pharmacological inhibitors of glycogen synthase kinase 3.
        Trends Pharmacol Sci. 2004; 25: 471-480
        • Bao S
        • Wu Q
        • Sathornsumetee S
        • et al.
        Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor.
        Cancer Res. 2006; 66: 7843-7848
        • Clarke MF
        • Dick JE
        • Dirks PB
        • et al.
        Cancer stem cells–perspectives on current status and future directions: AACR Workshop on Cancer Stem Cells.
        Cancer Res. 2006; 66: 9339-9344
        • Locker GY
        • Hamilton S
        • Harris J
        • et al.
        ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer.
        J Clin Oncol. 2006; 24: 5313-5327
        • Barrier A
        • Boelle PY
        • Roser F
        • et al.
        Stage II colon cancer prognosis prediction by tumor gene expression profiling.
        J Clin Oncol. 2006; 24: 4685-4691
        • Boyer J
        • Allen WL
        • McLean EG
        • et al.
        Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer.
        Cancer Res. 2006; 66: 2765-2777
        • Eschrich S
        • Yang I
        • Bloom G
        • et al.
        Molecular staging for survival prediction of colorectal cancer patients.
        J Clin Oncol. 2005; 23: 3526-3535

      Article info

      Publication history

      Accepted: November 21, 2007
      Received in revised form: November 20, 2007
      Received: October 10, 2007

      Identification

      DOI: https://doi.org/10.3816/CCC.2008.s.005

      Copyright

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

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