Journal Mobile Options
Table of Contents
Vol. 25, No. 1, 2007
Issue release date: March 2007
Section title: Review Article
Dig Dis 2007;25:67–75
(DOI:10.1159/000099172)

Adjuvant Chemotherapy for Colon Cancer: Evidence on Improvement in Survival

Samantas E.a · Dervenis C.b · Rigatos S.K.a
aThird Oncology Department, ‘Agii Anargiri’ Cancer Hospital, and bFirst Department of Surgery, ‘Agia Olga’ Hospital, Athens, Greece
email Corresponding Author

Abstract

Clear progress has been made in the adjuvant treatment of colon cancer. Until very recently, the absolute benefit for survival obtained with the administration of 6 months’ FU/LV compared with control was about 6%. Fluoropyrimidines have been shown to be at least as active and can replace intravenous FU/LV in stage III colon cancer. Based on the results of the MOSAIC and NSABP C-07 trials, the addition of oxaliplatin to FU/LV improves disease-free survival and FOLFOX for 6 months can be recommended as adjuvant treatment for patients with stage III colon cancer. The benefit of adjuvant chemotherapy in stage II disease is limited and it should be proposed in patients with high-risk features. Adjuvant treatment of colon cancer improving and the use of genetic/molecular markers with the new targeted therapies may further improve survival.

© 2007 S. Karger AG, Basel


  

Key Words

  • Colon cancer
  • Adjuvant chemotherapy
  • Fluoropyrimidines

References

  1. GLOBOCAN: Cancer Incidence Mortality and Prevalence Worldwide. Version IARC CancerBase No 5. Lyon, IARC Press, 2001.
  2. Obrand DI, Gordon PH: Incidence and pattern of recurrence following curative resection for colorectal carcinoma. Dis Colon Rectum 1997;40:15–24.
  3. American Joint Committee on Cancer: Cancer Staging Manual, ed 6. New York, Springer, 2002.
  4. Sashiro S: Recurrence pattern after curative resection of colorectal cancer in patients followed for a minimum of 10 years. Hepatogastroenterology 2003;50:1362–1366.

    External Resources

  5. Sargent DJ, Wieand S, Benedeui J, et al: Disease-free survival vs. overall survival as a primary endpoint for adjuvant colon cancer studies. Individual patient data from 12,915 patients on 15 randomized trials. J Clin Oncol 2004;22(suppl):245, abstr 3502.
  6. Wolmark N, Fischer B, Rockette H, et al: Postoperative adjuvant chemotherapy or BCG for colon cancer: results from NSABP C-01. J Natl Cancer Inst 1988;80:30–36.
  7. Laurie JA, Moertel CG, Fleming TR, et al: Surgical adjuvant therapy of large-bowel carcinoma: an evaluation of levamisole and the combination of levamisole and fluorouracil. The North Central Treatment Group and the Mayo Clinic. J Clinic Oncol 1989;7:1447–1456.
  8. Windle R, Bell PR, Shaw D: Five-year results of a randomized trial of adjuvant 5-fluorouracil and levamisole in colorectal cancer. Br J Surg 1987;74:569–572.
  9. 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.
  10. Moertel CG, Fleming TR, Macdonald JS, et al: Fluorouracil + levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Ann Intern Med 1995;122:321–326.
  11. Francini G, Petrioli R, Lorenzini L, et al: Folinic acid and 5-fluorouracil as adjuvant chemotherapy in colon cancer. Gastroenterology 1994;106:899–906.
  12. O’Connell MJ, Mailliard JA, Kahn MJ, et al: Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer. J Clin Oncol 1997;15:246–250.
  13. International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) Investigators: Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. Lancet 1995;345:939.
  14. Taal BG, Van Tinteren H, Zoetmulder FA: Adjuvant 5-FU + levamisole in colonic or rectal cancer: improved survival in stage II and III. Br J Cancer 2001;85:1437–1443.
  15. O’Connell MJ, Laurie JA, Kahn M, et al: Prospectively randomized trial of postoperative adjuvant chemotherapy in patients with high-risk colon cancer. J Clin Oncol 1998;16:295–300.
  16. Wolmark N, Rockette H, Fisher B, et al: The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Breast and Bowel Project C-03. J Clinic Oncol 1993;11:1879–1887.
  17. Wolmark N, Rockette H, Mamounas E, et al: Clinical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes’ B and C carcinoma of the colon: results from the National Surgical Breast and Bowel Project C-04. J Clin Oncol 1999;17:3533–3559.
  18. Wolmark N, Bryant J, Smith R, et al: Adjuvant 5-fluorouracil and leucovorin with or without interferon alfa-2a in colon carcinoma: Surgical Breast and Bowel Project C-05. J Natl Cancer Inst 1998;90:1810–1816.
  19. QUASAR Collaborative Group: Comparison of fluorouracil with additional levamisole, higher-dose folinic acid, or both, as adjuvant chemotherapy for colorectal cancer: a randomized trial. Lancet 2000;355:1588–1596.
  20. Porschen R, Bermann A, Loffler T, et al: Fluorouracil + leucovorin as effective adjuvant chemotherapy in curatively resected stage III colon cancer: results of the trial adjCCA-01. J Clin Oncol 2001;19:1787–1794.
  21. Haller DG, Catalano PJ, MacDonald JS, Mayer RJ: Fluorouracil, leucovorin and levamisole adjuvant therapy for colon cancer: five-year final report of Int-0089. Proc Am Soc Clin Oncol 1998;17:256A.
  22. Andre T, Colin P, Louvet C, et al: Semimonthly versus monthly regimen of fluorouracil and leucovorin administered for 24 or 36 weeks as adjuvant therapy in stage II and III colon cancer. J Clin Oncol 2003;21:2896–2903.
  23. Poplin EA, Benedetti JK, Estes NC, et al: Phase III Southwest Oncology Group 9415/Intergroup 0153 randomized trial of fluorouracil, leucovorin, and levamisole versus fluorouracil continuous infusion, and levamisole for adjuvant treatment of stage III and high-risk stage II colon cancer. J Clin Oncol 2005;23:1819–1825.
  24. Andre T, Quinaux E, Louvet C, et al: Updated results at 6 years of the GERCOR C96. 1. A phase III study comparing LV5FU2 to monthly 5-FU-leucovorin as adjuvant treatment for Dukes’ B2 and C colon cancer patients (abstract). J Clin Oncol 2005;23:250S.
  25. Gill S, Loprinzi CL, Sargent DJ, et al: Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: Who benefits and by how much? J Clin Oncol 2004;22:1797–1806.
  26. Twelves C, Wond A, Nowacki M, et al: Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 2005;352:2696–2704.
  27. Wolmark N, Wieand S, Lembersky B, et al: A phase III trial comparing oral UFT to FULV in stage II and III carcinoma of the colon: results of NSABP Protocol C-06. Proc Am Soc Clin Oncol 2004;22:247S.
  28. Sakamoto J, Ohashi Y, Hamada C, et al: Efficacy of oral adjuvant therapy after resection of colorectal cancer: 5-year results from thee randomized trials. J Clin Oncol 2004;22:484–492.

    External Resources

  29. Andre T, Boni C, Mounedji-BoudiafL, et al: Oxaliplatin, fluorouracil and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004;350:2343–2351.
  30. De Gramont A, Boni C, Navarro M, et al: Oxaliplatin/5-FU/LV in the adjuvant treatment of stage II and III colon cancer: efficacy results with a median follow-up of 4 years. J Clin Oncol 2005;23:246S.
  31. Wolmark N, Wieand SH, Kuebler J, et al: A phase III trial comparing FULV + oxaliplatin in stage II or II carcinoma of the colon: results of NSABP protocol C-07. J Clin Oncol 2005;23:246S.
  32. Rothenberg M, Meropol N, Poplin E, et al: Mortality associated with irinotecan + bolus fluorouracil/leucovorin: summary findings of an independent panel. J Clin Oncol 2001;19:3801–3807.
  33. Saltz L, Niedwiecki D, Hollis D, et al: Irinotecan + fluorouracil/leucovorin versus fluorouracil/leucovorin in stage III colon cancer (intergroup trial CALGB C89903). J Clin Oncol 2004;22:245S.

    External Resources

  34. Ychou M, Raoul JL, Douillard JY, et al: A phase III randomized trial of LV5FU2 + CP-11 vs. LV5FU2 alone in adjuvant high risk colon cancer (FNCLCC Accord02/FFCD9802). J Clin Oncol 2005;23:246S.
  35. Van Custem E, Labianca D, Hossfeld D, et al: Randomized phase III trial comparing infused irinotecan/5-fluorouracil/folinic acid vs. 5-FU/FA in stage III colon cancer patients. J Clin Oncol 2005;23:LBA8.

    External Resources

  36. Cunningham D, Humblet Y, Siena S, et al: Cetuximab monotherapy and cetuximab + irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004;351:337–345.
  37. Hurwitz H, Fehrenbacher L, Novotny W, et al: Bevacizumab + irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350:2335–2342.
  38. Nordlinger B, Rougier P, Arnaud JC, et al: Adjuvant regional chemotherapy and systemic chemotherapy versus systemic chemotherapy alone in patients with stage II-III colorectal cancer: a multicentre randomized controlled phase III trial. Lancet Oncol 2005;6:459–468.
  39. Mamounas E, Wieand S, Wolmark N, et al: Comparative efficacy of adjuvant chemotherapy in patients with Dukes’ C colon cancer: results from four National Surgical Adjuvant Breast and Bowel Project adjuvant studies (C-01, C-02, C-03, and C-04). J Clin Oncol 1999;17:1349–1355.
  40. International Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) Investigators: Efficacy of adjuvant fluorouracil and folinic acid in B2 colon cancer. J Clin Oncol 1999;17:1356–1363.

    External Resources

  41. Gray RG, Barnwell J, Hills R, et al: QUASAR a randomized study of adjuvant chemotherapy vs. observation including 3,238 colorectal cancer patients (abstract). Proc Am Soc Clin Oncol 2004;22:3501.
  42. Hickish T, Boni M, Navarro M, et al: FOLFOX-4 as adjuvant treatment for stage II colon cancer: subpopulation data from the MOSAIC trial (abstract). Proc Am Soc Clin Oncol 2004;23:275.
  43. Benson 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.
  44. Fearon ER, Cho KR, Nigro JM, et al: Identification of a chromosome 18q gene that is altered in colorectal cancers. Science 1990;247:49–56.
  45. Gryfe R, Kim H, Hsieh ET, et al: Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med 2000;342:69–77.
  46. Elsaleh H, Shannon B, Iacopetta B: Microsatellite instability as a molecular marker for very good survival in colorectal cancer patients receiving adjuvant chemotherapy. Gastroenterology 2001;120:1309–1310.
  47. Elsaleh H, Iacopetta B: Microsatellite instability is a predictive marker for survival benefit from adjuvant chemotherapy in a population-based series of stage III colorectal carcinoma. Clin Colorectal Cancer 2001;1:104–109.
  48. Ribic CM, Sargent DJ, Moore MJ, et al: Tumor microsatellite-instability status as predictor of from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 2003;349:247–257.
  49. Iyer L, Das S, Janisch L, et al: UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity. Pharmacogenomics J 2002;2:43–47.

  

Author Contacts

Dr. E. Samantas
3rd Oncology Department, ‘Agii Anargiri’ Cancer Hospital
Hassias Av. 9th Station
GR–131 22 Athens (Greece)
Tel./Fax +30 210 238 8798, E-Mail hecogaga@otenet.gr

  

Article Information

Number of Print Pages : 9
Number of Figures : 0, Number of Tables : 4, Number of References : 49

  

Publication Details

Digestive Diseases (Clinical Reviews)

Vol. 25, No. 1, Year 2007 (Cover Date: March 2007)

Journal Editor: Malfertheiner, P. (Magdeburg)
ISSN: 0257–2753 (print), 1421–9875 (Online)

For additional information: http://www.karger.com/DDI


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. GLOBOCAN: Cancer Incidence Mortality and Prevalence Worldwide. Version IARC CancerBase No 5. Lyon, IARC Press, 2001.
  2. Obrand DI, Gordon PH: Incidence and pattern of recurrence following curative resection for colorectal carcinoma. Dis Colon Rectum 1997;40:15–24.
  3. American Joint Committee on Cancer: Cancer Staging Manual, ed 6. New York, Springer, 2002.
  4. Sashiro S: Recurrence pattern after curative resection of colorectal cancer in patients followed for a minimum of 10 years. Hepatogastroenterology 2003;50:1362–1366.

    External Resources

  5. Sargent DJ, Wieand S, Benedeui J, et al: Disease-free survival vs. overall survival as a primary endpoint for adjuvant colon cancer studies. Individual patient data from 12,915 patients on 15 randomized trials. J Clin Oncol 2004;22(suppl):245, abstr 3502.
  6. Wolmark N, Fischer B, Rockette H, et al: Postoperative adjuvant chemotherapy or BCG for colon cancer: results from NSABP C-01. J Natl Cancer Inst 1988;80:30–36.
  7. Laurie JA, Moertel CG, Fleming TR, et al: Surgical adjuvant therapy of large-bowel carcinoma: an evaluation of levamisole and the combination of levamisole and fluorouracil. The North Central Treatment Group and the Mayo Clinic. J Clinic Oncol 1989;7:1447–1456.
  8. Windle R, Bell PR, Shaw D: Five-year results of a randomized trial of adjuvant 5-fluorouracil and levamisole in colorectal cancer. Br J Surg 1987;74:569–572.
  9. 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.
  10. Moertel CG, Fleming TR, Macdonald JS, et al: Fluorouracil + levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Ann Intern Med 1995;122:321–326.
  11. Francini G, Petrioli R, Lorenzini L, et al: Folinic acid and 5-fluorouracil as adjuvant chemotherapy in colon cancer. Gastroenterology 1994;106:899–906.
  12. O’Connell MJ, Mailliard JA, Kahn MJ, et al: Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer. J Clin Oncol 1997;15:246–250.
  13. International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) Investigators: Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. Lancet 1995;345:939.
  14. Taal BG, Van Tinteren H, Zoetmulder FA: Adjuvant 5-FU + levamisole in colonic or rectal cancer: improved survival in stage II and III. Br J Cancer 2001;85:1437–1443.
  15. O’Connell MJ, Laurie JA, Kahn M, et al: Prospectively randomized trial of postoperative adjuvant chemotherapy in patients with high-risk colon cancer. J Clin Oncol 1998;16:295–300.
  16. Wolmark N, Rockette H, Fisher B, et al: The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Breast and Bowel Project C-03. J Clinic Oncol 1993;11:1879–1887.
  17. Wolmark N, Rockette H, Mamounas E, et al: Clinical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes’ B and C carcinoma of the colon: results from the National Surgical Breast and Bowel Project C-04. J Clin Oncol 1999;17:3533–3559.
  18. Wolmark N, Bryant J, Smith R, et al: Adjuvant 5-fluorouracil and leucovorin with or without interferon alfa-2a in colon carcinoma: Surgical Breast and Bowel Project C-05. J Natl Cancer Inst 1998;90:1810–1816.
  19. QUASAR Collaborative Group: Comparison of fluorouracil with additional levamisole, higher-dose folinic acid, or both, as adjuvant chemotherapy for colorectal cancer: a randomized trial. Lancet 2000;355:1588–1596.
  20. Porschen R, Bermann A, Loffler T, et al: Fluorouracil + leucovorin as effective adjuvant chemotherapy in curatively resected stage III colon cancer: results of the trial adjCCA-01. J Clin Oncol 2001;19:1787–1794.
  21. Haller DG, Catalano PJ, MacDonald JS, Mayer RJ: Fluorouracil, leucovorin and levamisole adjuvant therapy for colon cancer: five-year final report of Int-0089. Proc Am Soc Clin Oncol 1998;17:256A.
  22. Andre T, Colin P, Louvet C, et al: Semimonthly versus monthly regimen of fluorouracil and leucovorin administered for 24 or 36 weeks as adjuvant therapy in stage II and III colon cancer. J Clin Oncol 2003;21:2896–2903.
  23. Poplin EA, Benedetti JK, Estes NC, et al: Phase III Southwest Oncology Group 9415/Intergroup 0153 randomized trial of fluorouracil, leucovorin, and levamisole versus fluorouracil continuous infusion, and levamisole for adjuvant treatment of stage III and high-risk stage II colon cancer. J Clin Oncol 2005;23:1819–1825.
  24. Andre T, Quinaux E, Louvet C, et al: Updated results at 6 years of the GERCOR C96. 1. A phase III study comparing LV5FU2 to monthly 5-FU-leucovorin as adjuvant treatment for Dukes’ B2 and C colon cancer patients (abstract). J Clin Oncol 2005;23:250S.
  25. Gill S, Loprinzi CL, Sargent DJ, et al: Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: Who benefits and by how much? J Clin Oncol 2004;22:1797–1806.
  26. Twelves C, Wond A, Nowacki M, et al: Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 2005;352:2696–2704.
  27. Wolmark N, Wieand S, Lembersky B, et al: A phase III trial comparing oral UFT to FULV in stage II and III carcinoma of the colon: results of NSABP Protocol C-06. Proc Am Soc Clin Oncol 2004;22:247S.
  28. Sakamoto J, Ohashi Y, Hamada C, et al: Efficacy of oral adjuvant therapy after resection of colorectal cancer: 5-year results from thee randomized trials. J Clin Oncol 2004;22:484–492.

    External Resources

  29. Andre T, Boni C, Mounedji-BoudiafL, et al: Oxaliplatin, fluorouracil and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004;350:2343–2351.
  30. De Gramont A, Boni C, Navarro M, et al: Oxaliplatin/5-FU/LV in the adjuvant treatment of stage II and III colon cancer: efficacy results with a median follow-up of 4 years. J Clin Oncol 2005;23:246S.
  31. Wolmark N, Wieand SH, Kuebler J, et al: A phase III trial comparing FULV + oxaliplatin in stage II or II carcinoma of the colon: results of NSABP protocol C-07. J Clin Oncol 2005;23:246S.
  32. Rothenberg M, Meropol N, Poplin E, et al: Mortality associated with irinotecan + bolus fluorouracil/leucovorin: summary findings of an independent panel. J Clin Oncol 2001;19:3801–3807.
  33. Saltz L, Niedwiecki D, Hollis D, et al: Irinotecan + fluorouracil/leucovorin versus fluorouracil/leucovorin in stage III colon cancer (intergroup trial CALGB C89903). J Clin Oncol 2004;22:245S.

    External Resources

  34. Ychou M, Raoul JL, Douillard JY, et al: A phase III randomized trial of LV5FU2 + CP-11 vs. LV5FU2 alone in adjuvant high risk colon cancer (FNCLCC Accord02/FFCD9802). J Clin Oncol 2005;23:246S.
  35. Van Custem E, Labianca D, Hossfeld D, et al: Randomized phase III trial comparing infused irinotecan/5-fluorouracil/folinic acid vs. 5-FU/FA in stage III colon cancer patients. J Clin Oncol 2005;23:LBA8.

    External Resources

  36. Cunningham D, Humblet Y, Siena S, et al: Cetuximab monotherapy and cetuximab + irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004;351:337–345.
  37. Hurwitz H, Fehrenbacher L, Novotny W, et al: Bevacizumab + irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350:2335–2342.
  38. Nordlinger B, Rougier P, Arnaud JC, et al: Adjuvant regional chemotherapy and systemic chemotherapy versus systemic chemotherapy alone in patients with stage II-III colorectal cancer: a multicentre randomized controlled phase III trial. Lancet Oncol 2005;6:459–468.
  39. Mamounas E, Wieand S, Wolmark N, et al: Comparative efficacy of adjuvant chemotherapy in patients with Dukes’ C colon cancer: results from four National Surgical Adjuvant Breast and Bowel Project adjuvant studies (C-01, C-02, C-03, and C-04). J Clin Oncol 1999;17:1349–1355.
  40. International Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) Investigators: Efficacy of adjuvant fluorouracil and folinic acid in B2 colon cancer. J Clin Oncol 1999;17:1356–1363.

    External Resources

  41. Gray RG, Barnwell J, Hills R, et al: QUASAR a randomized study of adjuvant chemotherapy vs. observation including 3,238 colorectal cancer patients (abstract). Proc Am Soc Clin Oncol 2004;22:3501.
  42. Hickish T, Boni M, Navarro M, et al: FOLFOX-4 as adjuvant treatment for stage II colon cancer: subpopulation data from the MOSAIC trial (abstract). Proc Am Soc Clin Oncol 2004;23:275.
  43. Benson 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.
  44. Fearon ER, Cho KR, Nigro JM, et al: Identification of a chromosome 18q gene that is altered in colorectal cancers. Science 1990;247:49–56.
  45. Gryfe R, Kim H, Hsieh ET, et al: Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med 2000;342:69–77.
  46. Elsaleh H, Shannon B, Iacopetta B: Microsatellite instability as a molecular marker for very good survival in colorectal cancer patients receiving adjuvant chemotherapy. Gastroenterology 2001;120:1309–1310.
  47. Elsaleh H, Iacopetta B: Microsatellite instability is a predictive marker for survival benefit from adjuvant chemotherapy in a population-based series of stage III colorectal carcinoma. Clin Colorectal Cancer 2001;1:104–109.
  48. Ribic CM, Sargent DJ, Moore MJ, et al: Tumor microsatellite-instability status as predictor of from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 2003;349:247–257.
  49. Iyer L, Das S, Janisch L, et al: UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity. Pharmacogenomics J 2002;2:43–47.