New Agents for Colorectal Cancer

Authors:
Mary F. MulcahyFrom Division of Hematology and Oncology/Department of Medicine, Feinberg School of Medicine, Northwestern University, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois.

Search for other papers by Mary F. Mulcahy in
Current site
Google Scholar
PubMedClose
 MD
and
Al B. Benson IIIFrom Division of Hematology and Oncology/Department of Medicine, Feinberg School of Medicine, Northwestern University, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois.

Search for other papers by Al B. Benson III in
Current site
Google Scholar
PubMedClose
 MD
Volume/Issue:
Volume 1: Issue 1
Online Publication Date:
Mar 2003
DOI:
https://doi.org/10.6004/jnccn.2003.0013
Full access

The past 5 years have seen significant developments in the treatment of colorectal cancer (CRC). New chemotherapy agents with activity in CRC have demonstrated an improvement in survival for patients with advanced CRC. Studies now are focusing on combinations and sequences of chemotherapy agents to prolong survival in second- and even third-line therapies. Oral agents have been developed and are being studied in combination chemotherapy regimens. Development of oral combinations should maintain a survival advantage with the added benefit of convenience for the patient. Drugs designed to act on specific cellular protein targets have also shown activity and are being explored further. Researchers continue to pursue immunotherapy and vaccine therapy. Studies are now focusing on how best to use the available agents. These new agents and new combinations of agents and of approaches have led and should continue to lead to improved outcomes in the treatment of patients with CRC.

Correspondence: Mary F. Mulcahy, Northwestern University, Division of Hematology and Oncology/Department of Medicine, Feinberg School of Medicine, Northwestern University Robert H. Lurie Comprehensive Cancer Center, 676 North Saint Clair, Suite 850, Chicago, IL 60611. E-mail: m-mulcahy@northwestern.edu
  • Collapse
  • Expand
  • 1

    Greenlee RT, Hill-Harmon MB, Murray T et al.. Cancer statistics, 2001. CA Cancer J Clin 2001;51:15–36.

  • 2

    Leichman CG, Fleming TR, Muggia FM et al.. Phase II study of fluorouracil and its modulation in advanced colorectal cancer: A Southwest Oncology Group study. J Clin Oncol 1995;13:1303–1311.

    • Search Google Scholar
    • Export Citation
  • 3

    Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer: Meta-analysis group in cancer. J Clin Oncol 1998;16:301–308.

    • Search Google Scholar
    • Export Citation
  • 4

    O'Dwyer PJ, Manola J, Valone FH et al.. Fluorouracil modulation in colorectal cancer: Lack of improvement with N-phosphonoacetyl-l-aspartic acid or oral leucovorin or interferon, but enhanced therapeutic index with weekly 24-hour infusion schedule: An Eastern Cooperative Oncology Group/Cancer and Leukemia Group B Study. J Clin Oncol 2001;19:2413–2421.

    • Search Google Scholar
    • Export Citation
  • 5

    de Gramont A, Bosset JF, Milan C et al.. Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: A French intergroup study. J Clin Oncol 1997; 15:808–815.

    • Search Google Scholar
    • Export Citation
  • 6

    Cunningham D, Pyrhonen S, James RD et al.. Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet 1998;352:1413–1418.

    • Search Google Scholar
    • Export Citation
  • 7

    Rougier P, Van Cutsem E, Bajetta E et al.. Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. Lancet 1998;352:1407–1412.

    • Search Google Scholar
    • Export Citation
  • 8

    Saltz LB, Cox JV, Blanke C et al.. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer: Irinotecan Study Group. N Engl J Med 2000; 343:905–914.

    • Search Google Scholar
    • Export Citation
  • 9

    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.

    • Search Google Scholar
    • Export Citation
  • 10

    Machover D, Diaz-Rubio E, de Gramont A et al.. Two consecutive phase II studies of oxaliplatin (L-OHP) for treatment of patients with advanced colorectal carcinoma who were resistant to previous treatment with fluoropyrimidines. Ann Oncol 1996;7:95–98.

    • Search Google Scholar
    • Export Citation
  • 11

    Levi F, Perpoint B, Garufi C et al.. Oxaliplatin activity against metastatic colorectal cancer: A phase II study of 5-day continuous venous infusion at circadian rhythm modulated rate. Eur J Cancer 1993;29A:1280–1284.

    • Search Google Scholar
    • Export Citation
  • 12

    Diaz-Rubio E, Sastre J, Zaniboni A et al.. Oxaliplatin as single agent in previously untreated colorectal carcinoma patients: A phase II multicentric study. Ann Oncol 1998; 9:105–108.

    • Search Google Scholar
    • Export Citation
  • 13

    Becouarn Y, Ychou M, Ducreux M et al.. Phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients: Digestive Group of French Federation of Cancer Centers. J Clin Oncol 1998;16:2739–2744.

    • Search Google Scholar
    • Export Citation
  • 14

    Raymond E, Buquet-Fagot C, Djelloul S et al.. Antitumor activity of oxaliplatin in combination with 5-fluorouracil and the thymidylate synthase inhibitor AG337 in human colon, breast and ovarian cancers. Anticancer Drugs 1997;8:876–885.

    • Search Google Scholar
    • Export Citation
  • 15

    Giacchetti S, Perpoint B, Zidani R et al.. Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol 2000;18:136–147.

    • Search Google Scholar
    • Export Citation
  • 16

    de Gramont A, Figer A, Seymour M et al.. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000;18: 2938–2947.

    • Search Google Scholar
    • Export Citation
  • 17

    Grothey A, Buechele T, Kroening H et al.. Phase III trial of bolus 5-fluorouracil (5-FU)/folinic acid (FA) (MAYO) vs. weekly oxaliplatin (OXA) plus high dose 24h 5-FU infusion/FA in patients with advanced colorectal cancer (CRC) [abstract]. Eur J Cancer 2001;37(suppl 6):257.

    • Search Google Scholar
    • Export Citation
  • 18

    de Gramont A, Vignoud J, Tournigand C et al.. Oxaliplatin with high-dose leucovorin and 5-fluorouracil 48-hour continuous infusion in pretreated metastatic colorectal cancer. Eur J Cancer 1997;33:214–219.

    • Search Google Scholar
    • Export Citation
  • 19

    Crawford LM Jr. Drug for colorectal cancer. JAMA 2002;288:1225.

  • 20

    Goldberg RM, Morton RF, Sargent DJ et al.. N9741: Oxaliplatin (Oxal) or CPT-11 + 5-fluorouracil (5-FU)/leucovorin (LV) or oxal + CPT-11 in advanced colorectal cancer (CRC): Initial toxicity and response data from a GI intergroup study [abstract]. Proceedings of the American Society of Clinical Oncology. May 18–21, 2002;21.

    • Search Google Scholar
    • Export Citation
  • 21

    Morton RF, Goldberg RM, Sargent DJ et al.. Oxaliplatin (OXAL) or CPT-11 combined with 5FU/leucovorin (LV) in advanced colorectal cancer (CRC): An NCCTG/CALGB study [abstract]. Proceedings of the American Society of Clinical Oncology. May 12–15, 2001;19.

    • Search Google Scholar
    • Export Citation
  • 22

    Rothenberg ML, Meropol NJ, Poplin EA et al.. Mortality associated with irinotecan plus bolus fluorouracil/leucovorin: Summary findings of an independent panel. J Clin Oncol 2001;19:3801–3807.

    • Search Google Scholar
    • Export Citation
  • 23

    Tournigand C, Louvet C, Quinaux E et al.. FOLFIRI followed by FOLFOX versus FOLFOX followed by FOLFIRI in metastatic colorectal cancer (MCRC): Final results of a phase III study [abstract]. Proceedings of the American Society of Clinical Oncology May 12-15, 2001;20.

    • Search Google Scholar
    • Export Citation
  • 24

    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.

    • Search Google Scholar
    • Export Citation
  • 25

    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.

    • Search Google Scholar
    • Export Citation
  • 26

    Shields AF, Zalupski MM, Marshall JL, Meropol NJ. A phase II trial of oxaliplatin and capecitabine in patients with advanced colorectal cancer [abstract]. Proceedings of the American Society of Clinical Oncology. May 18–21, 2002;21.

    • Search Google Scholar
    • Export Citation
  • 27

    Tabernero J, Butts C, Cassidy J et al.. Capecitabine and oxaliplatin in xombination as first-line therapy for patients (pts) with metastatic colorectal cancer (MCRC): Results of an international multicenter phase II trial [abstract]. Proceedings of the American Society of Clinical Oncology. May 18–21, 2002; 21.

    • Search Google Scholar
    • Export Citation
  • 28

    Schilsky RL, Levin J, West WH et al.. Randomized, open-label, phase III study of a 28-day oral regimen of eniluracil plus fluorouracil versus intravenous fluorouracil plus leucovorin as first-line therapy in patients with metastatic/advanced colorectal cancer. J Clin Oncol 2002;20:1519–1526.

    • Search Google Scholar
    • Export Citation
  • 29

    Van Cutsem E, Sorensen J, Cassidy J et al.. International phase III study of oral eniluracil (EU) plus 5-fluorouracil (5-FU) versus intravenous (IV) 5-FU plus leucovorin (LV) in the treatment of advanced colorectal cancer (ACC) [abstract]. Proceedings of the American Society of Clinical Oncology May 12–15, 2001;20.

    • Search Google Scholar
    • Export Citation
  • 30

    Douillard JY, Hoff PM, Skillings JR et al.. Multicenter phase III study of uracil/tegafur and oral leucovorin versus fluorouracil and leucovorin in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2002;20: 3605–3616.

    • Search Google Scholar
    • Export Citation
  • 31

    FDA's handling of UFT raises questions about agency's isolation, grasp of science. Cancer Lett 2000;26:1–12.

  • 32

    Ohtsu A, Baba H, Sakata Y et al.. Phase II study of S-1, a novel oral fluorophyrimidine derivative, in patients with metastatic colorectal carcinoma: S-1 Cooperative Colorectal Carcinoma Study Group. Br J Cancer 2000;83:141–145.

    • Search Google Scholar
    • Export Citation
  • 33

    Wolmark N, Fisher B, Rockette H et al.. Postoperative adjuvant chemotherapy or BCG for colon cancer: results from NSABP protocol C-01. J Natl Cancer Inst 1988;80:30–36.

    • Search Google Scholar
    • Export Citation
  • 34

    Harris JE, Ryan L, Hoover HC Jr et al.. Adjuvant active specific immunotherapy for stage II and III colon cancer with an autologous tumor cell vaccine: Eastern Cooperative Oncology Group Study E5283. J Clin Oncol 2000;18: 148–157.

    • Search Google Scholar
    • Export Citation
  • 35

    LoBuglio AF, Saleh MN, Lee J et al.. Phase I trial of multiple large doses of murine monoclonal antibody CO17-1A. I. Clinical aspects. J Natl Cancer Inst 1988;80:932–936.

    • Search Google Scholar
    • Export Citation
  • 36

    Riethmuller G, Schneider-Gadicke E, Schlimok G et al.. Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma: German Cancer Aid 17-1A Study Group. Lancet 1994;343:1177–1183.

    • Search Google Scholar
    • Export Citation
  • 37

    Riethmuller G, Holz E, Schlimok G et al.. Monoclonal antibody therapy for resected Dukes' C colorectal cancer: Seven-year outcome of a multicenter randomized trial. J Clin Oncol 1998;16:1788–1794.

    • Search Google Scholar
    • Export Citation
  • 38

    Moertel CG, Fleming TR, Macdonald JS et al.. Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med 1990;322:352–358.

    • Search Google Scholar
    • Export Citation
  • 39

    Punt CJ, Nagy A, Douillard JY et al.. Edrecolomab (17-1A antibody) alone or in combination with 5-fluorouracil based chemotherapy in the adjuvant treatment of stage III colon cancer: Results of a phase III study [abstract]. Proceedings of the American Society of Clinical Oncology. May 12–15, 2001;20.

    • Search Google Scholar
    • Export Citation
  • 40

    Fields ALA, Keller AM, Schwartzberg L et al.. Edrecolomab (17-1A antibody) (EDR) in combination with 5-flouruoracil (FU) based chemotherapy in the adjuvant treatment of stage III colon cancer: Results of a randomised North American phase III study [abstract]. Proceedings of the American Society of Clinical Oncology. May 18–21, 2002;21.

    • Search Google Scholar
    • Export Citation
  • 41

    Foon KA, John WJ, Chakraborty M et al.. Clinical and immune responses in resected colon cancer patients treated with anti-idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen. J Clin Oncol 1999;17:2889–2895.

    • Search Google Scholar
    • Export Citation
  • 42

    Foon KA, John WJ, Chakraborty M et al.. Clinical and immune responses in advanced colorectal cancer patients treated with anti-idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen. Clin Cancer Res 1997; 3:1267–1276.

    • Search Google Scholar
    • Export Citation
  • 43

    Salomon DS, Brandt R, Ciardiello F et al.. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 1995;19:183–232.

    • Search Google Scholar
    • Export Citation
  • 44

    Messa C, Russo F, Caruso MG et al.. EGF, TGF-alpha, and EGF-R in human colorectal adenocarcinoma. Acta Oncol 1998;37:285–289.

  • 45

    Mayer A, Takimoto M, Fritz E et al.. The prognostic significance of proliferating cell nuclear antigen, epidermal growth factor receptor, and mdr gene expression in colorectal cancer. Cancer 1993;71:2454–2460.

    • Search Google Scholar
    • Export Citation
  • 46

    Hemming AW, Davis NL, Kluftinger A et al.. Prognostic markers of colorectal cancer: An evaluation of DNA content, epidermal growth factor receptor, and Ki-67. J Surg Oncol 1992;51:147–152.

    • Search Google Scholar
    • Export Citation
  • 47

    Saltz L, 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) [abstract]. Proceedings of the American Society of Clinical Oncology May 12–15, 2001;20.

    • Search Google Scholar
    • Export Citation
  • 48

    Saltz L, Meropol NJ, Loehrer PJ et al.. Single agent IMC-225 (Erbitux) has activity in CPT-11 refractory colorectal cancer (CRC) that expresses the epidermal growth factor Receptor (EGFR) [abstract]. Proceedings of the American Society of Clinical Oncology May 12–15, 2002;21.

    • Search Google Scholar
    • Export Citation
  • 49

    Figlin RA, Belldegrun AS, Crawford J et al.. ABX-EGF, a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAB) in patients with advanced cancer: Phase I clinical results [abstract]. Proceedings of the American Society of Clinical Oncology May 18–21, 2002;21.

    • Search Google Scholar
    • Export Citation
  • 50

    Roskos L, Lohner M, Osborn K et al.. Low pharmacokinetic variability facilitates optimal dosing of ABX-EGF in cancer patients [abstract]. Proceedings of the American Society of Clinical Oncology 2002;21.

    • Search Google Scholar
    • Export Citation
  • 51

    Hammond LA, Figueroa J, Schwartzberg L et al.. Feasibility and pharmacokinetic (PK) trial of ZD 1839 (Iressa™), and epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), in combination with 5-fluroouracil (5-FU) and leucovorin (LV) in patients with advanced colorectal cancer [abstract]. Proceedings of the American Society of Clinical Oncology May 12–15, 2001;20; San Francisco.

    • Search Google Scholar
    • Export Citation
  • 52

    Hidalgo M, Siu LL, Nemunaitis J et al.. Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. J Clin Oncol 2001;19:3267–3279.

    • Search Google Scholar
    • Export Citation
  • 53

    Carmichael J, White JD, Kosuge DD et al.. Increased expression of vascular endothelial growth factor-D (VEGF-D) is associated with poor survival in colorectal cancer (CRC) [abstract]. Proceedings of the American Society of Clinical Oncology May 20–23, 2000;19; New Orleans.

    • Search Google Scholar
    • Export Citation
  • 54

    Bergsland EK, Fehrenbacher L, Novotny W et al.. Bevacizumab (BV) + chemotherapy (CT) may improve survival in metastatic colorectal cancer (MCRC) subjects with unfavorable prognostic indicators [abstract]. Proceedings of the American Society of Clinical Oncology May 20–23, 2000;19; New Orleans.

    • Search Google Scholar
    • Export Citation
  • 55

    Bergsland E, Hurwitz H, Fehrenbacher L, J et al.. A randomized phase II trial comparing rhuMAb VEGF (recombinant humanized monoclonal antibody to vascular endothelial cell growth factor) plus 5-fluorouracil/leucovorin (FU/LV) to FU/LV alone in patients with metastatic colorectal cancer [abstract]. Proceedings of the American Society of Clinical Oncology May 20–23, 2000;19; New Orleans.

    • Search Google Scholar
    • Export Citation
  • 56

    Eng C, Kindler HL, Stadler WM et al.. SU5416 in advanced colorectal cancer (CRC): A University of Chicago Phase II Consortium Study [abstract]. Proceedings of the American Society of Clinical Oncology May 12–15, 2001;20; San Francisco.

    • Search Google Scholar
    • Export Citation
  • 57

    Rosen PJ, Amado R, Hecht JR et al.. A phase I/II study of SU5416 in combination with 5-FU/leucovorin in patients with metastatic colorectal cancer [abstract]. Proceedings of the American Society of Clinical Oncology May 20–23, 2000;19; New Orleans.

    • Search Google Scholar
    • Export Citation
  • 58

    Rothenberg ML, Berlin JD, Cropp GF et al.. Phase I/II study of SU5416 in combination with ironotecan/5-FU/LV (IFL) in patients with metastatic colorectal cancer [abstract]. Proceedings of the American Society of Clinical Oncology May 12–15, 2001;20; San Francisco.

    • Search Google Scholar
    • Export Citation
  • 59

    Pharmacia's SU5416 not effective. Expert Rev Anticancer Ther 2002;2:5.

  • 60

    Tomozawa S, Tsuno NH, Sunami E et al.. Cyclooxygenase-2 overexpression correlates with tumour recurrence, especially haematogenous metastasis, of colorectal cancer. Br J Cancer 2000;83:324–328.

    • Search Google Scholar
    • Export Citation
  • 61

    Kawamori T, Rao CV, Seibert K, Reddy BS. Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res 1998;58:409–412.

    • Search Google Scholar
    • Export Citation
  • 62

    Steinbach G, Lynch PM, Phillips RK et al.. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 2000;342:1946–1952.

    • Search Google Scholar
    • Export Citation
  • 63

    Blanke C, Benson A III, Dragovich T et al.. A phase II trial of celecoxib (CX), irinotecan (I), 5-fluorouricil (5FU), and leucovorin (LCV) in patients (pts) with unresectable or metastatic colorectal cancer (CRC) [abstract]. Proceedings of the American Society of Clinical Oncology May 18–21, 2002;21; Orlando.

    • Search Google Scholar
    • Export Citation
  • 64

    Lin EH, Morris J, Chau NK et al.. Celecoxib-attenuated, capecitabine-induced hand-and-foot syndrome (HFS) and diarrhea and improved time to tumor progression in metastatic colorectal cancer (MCRC) [abstract]. Proceedings of the American Society of Clinical Oncology May 18–21, 2002;21; Orlando.

    • Search Google Scholar
    • Export Citation
Copyright:
Copyright © 2003 by the National Comprehensive Cancer Network 2003
Page Numbers:
12
Article Category:
Research Article
Received:
04 Sep 2002
Accepted:
18 Sep 2002
Print Publication Date:
01 Mar 2003
Online Publication Date:
Mar 2003
Keywords:
Colorectal cancer; chemotherapy; clinical trials; immunotherapy; molecular therapy
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 65 65 4
PDF Downloads 0 0 0
EPUB Downloads 0 0 0