Drugs & Aging

, Volume 20, Issue 1, pp 1–11

Colorectal Cancer in the Elderly

Is Palliative Chemotherapy of Value?
  • Friedemann Honecker
  • Claus-Henning Köhne
  • Carsten Bokemeyer
Current Opinion

Abstract

Colorectal cancer is a disease of the elderly, with 70% of patients being aged 65 years or older. In Western countries, the total number of elderly patients with this disease is expected to further increase in the future. Since the incidence of adverse physical or socioeconomic conditions in the elderly is higher than in younger patients, a thorough assessment of the patient’s suitability for therapy should be performed before a decision is made. Using a Comprehensive Geriatric Assessment (CGA) to subdivide the population of elderly cancer patients into three groups can help to guide treatment decisions. Both in the adjuvant and in the palliative setting, there are sufficient data supporting the use of fluorouracil-based chemotherapy in fit elderly patients who can tolerate cytotoxic treatment. Systemic chemotherapy has been shown to effectively reduce mortality in the adjuvant situation and to be of clinical benefit for patients with metastatic disease in terms of longer survival, control of symptoms and quality of life. In recent years, new substances such as oxaliplatin or irinotecan have shown significant activity in the treatment of patients with metastatic colorectal cancer. However, information on how to guide the use of these new drugs in elderly patients is still lacking. Limited data from clinical trials indicate treatment efficacy in selected elderly patients comparable to that observed in younger patients, with overall manageable toxicity. Clearly, further clinical trials in elderly patients with colorectal cancer are necessary as well as the incorporation of aspects of geriatric medicine into the teaching programme of medical oncologists.

References

  1. 1.
    Manton KG, Vaupel JW. Survival after the age of 80 in the United States, Sweden, France, England, and Japan. N Engl J Med 1995; 333: 1232–5PubMedCrossRefGoogle Scholar
  2. 2.
    Ries LA, Wingo PA, Miller DS, et al. The annual report to the nation on the status of cancer, 1973–1997, with a special section on colorectal cancer. Cancer 2000; 88: 2398–424PubMedCrossRefGoogle Scholar
  3. 3.
    Fentiman IS, Tirelli U, Monfardini S, et al. Cancer in the elderly: why so badly treated? Lancet 1990; 335: 1020–2PubMedCrossRefGoogle Scholar
  4. 4.
    Fentiman IS. Are the elderly receiving appropriate treatment for cancer? Ann Oncol 1996; 7: 657–8PubMedCrossRefGoogle Scholar
  5. 5.
    Hutchins LF, Unger JM, Crowley JJ, et al. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 1999; 341: 2061–7PubMedCrossRefGoogle Scholar
  6. 6.
    Balducci L, Corcoran MB. Antineoplastic chemotherapy of the older cancer patient. Hematol Oncol Clin North Am 2000; 14: 193–212PubMedCrossRefGoogle Scholar
  7. 7.
    Honecker F, Wedding U, Kolb G, et al. Chemotherapy of colorectal cancer: which therapy is justified for elderly patients? Onkologie 2001; 24: 87–94PubMedCrossRefGoogle Scholar
  8. 8.
    Köhne CH, Grothey A, Bokemeyer C, et al. Chemotherapy in elderly patients with colorectal cancer. Ann Oncol 2001; 12: 435–42PubMedCrossRefGoogle Scholar
  9. 9.
    Sargent DJ, Goldberg RM, Jacobson SD, et al. A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med 2001; 345: 1091–6PubMedCrossRefGoogle Scholar
  10. 10.
    Zalcberg J, Kerr D, Seymour L, et al. Haematological and nonhaematological toxicity after 5-fluorouracil and leucovorin in patients with advanced colorectal cancer is significantly associated with gender, increasing age and cycle number. Eur J Cancer 1998; 12: 1871–5CrossRefGoogle Scholar
  11. 11.
    Jacobson SD, Cha S, Sargent DJ, et al. Tolerability, dose intensity, and benefit of 5FU-based chemotherapy for advanced colorectal cancer (CRC) in the elderly: a North Central Cancer Treatment Group (NCCTG) study [abstract]. Proc Am Soc Clin Oncol 2001; 20: 384aGoogle Scholar
  12. 12.
    Extermann M. Measuring comorbidity in older cancer patients. Eur J Cancer 2000; 36: 453–71PubMedCrossRefGoogle Scholar
  13. 13.
    Bernabei R, Venturiero V, Tarsitani P, et al. The comprehensive geriatric assessment: when, where, how. Crit Rev Oncol Hematol 2000; 33: 45–56PubMedCrossRefGoogle Scholar
  14. 14.
    Balducci L, Extermann M. Management of cancer in the older person: a practical approach. Oncologist 2000; 5(3): 224–37PubMedCrossRefGoogle Scholar
  15. 15.
    Balducci L, Extermann M. Management of the frail person with advanced cancer. Crit Rev Oncol Hematol 2000; 33: 143–8PubMedCrossRefGoogle Scholar
  16. 16.
    Balducci L. Geriatric oncology: challenges for a new century. Eur J Cancer 2000; 36: 1741–54PubMedCrossRefGoogle Scholar
  17. 17.
    Parkin DM, Pisani P, Ferlay J. Global cancer statistics. CA Cancer J Clin 1999; 49: 33–64PubMedCrossRefGoogle Scholar
  18. 18.
    Nordic Gastrointestinal Tumor Adjuvant Therapy Group. Expectancy or primary chemotherapy in patients with advanced asymptomatic colorectal cancer: a randomized trial. J Clin Oncol 1992; 10: 904–11Google Scholar
  19. 19.
    Scheithauer W, Rosen H, Kornek GV, et al. Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer. BMJ 1993; 306: 752–5PubMedCrossRefGoogle Scholar
  20. 20.
    Cunningham D, Pyrhönen 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: 1413–8PubMedCrossRefGoogle Scholar
  21. 21.
    Simmonds PC. Palliative chemotherapy for advanced colorectal cancer: systematic review and meta-analysis. Colorectal Cancer Collaborative Group. BMJ 2000; 32: 531–5Google Scholar
  22. 22.
    Glimelius B, Graf W, Hoffman K, et al. General condition of asymptomatic patients with advanced colorectal cancer receiving palliative chemotherapy: a longitudinal study. Acta Oncol 1992; 31: 645–51PubMedCrossRefGoogle Scholar
  23. 23.
    Glimelius B, Hoffmann K, Graf W, et al. Cost-effectiveness of palliative chemotherapy in advanced gastrointestinal cancer. Ann Oncol 1995; 6(3): 267–74PubMedGoogle Scholar
  24. 24.
    Köhne CH, Cunningham D, Di Costanzo F, et al. Clinical determinants of survival in patients with 5-fluorouracil-based treatment for metastatic colorectal cancer: results of a multivariate analysis of 3825 patients. Ann Oncol 2002; 13(2): 308–17PubMedCrossRefGoogle Scholar
  25. 25.
    Stein BN, Petrelli NJ, Douglass HO, et al. Age and sex are independent predictors of 5-fluorouracil toxicity: analysis of a large scale phase III trial. Cancer 1995; 75: 11–7PubMedCrossRefGoogle Scholar
  26. 26.
    Cascinu S, Del Ferro E, Catalano G. Toxicity and therapeutic response to chemotherapy in patients aged 70 years or older with advanced cancer. Am J Clin Oncol 1996; 19: 371–4PubMedCrossRefGoogle Scholar
  27. 27.
    Chiara S, Nobile MT, Vincenti M, et al. Advanced colorectal cancer in the elderly: results of consecutive trials with 5-fluorouracil-based chemotherapy. Cancer Chemother Pharmacol 1998; 42: 336–40PubMedCrossRefGoogle Scholar
  28. 28.
    Popescu RA, Norman A, Ross PJ, et al. Adjuvant or palliative chemotherapy for colorectal cancer in patients 70 years or older. J Clin Oncol 1999; 17: 2412–8PubMedGoogle Scholar
  29. 29.
    Milano G, Etienne MC, Pierrefite V, et al. Dihydropyrimidine dehydrogenase deficiency and fluorouracil-related toxicity. Br J Cancer 1999; 79: 627–30PubMedCrossRefGoogle Scholar
  30. 30.
    Sloan JA, Goldberg RM, Sargent DJ, et al. Women experience greater toxicity with fluorouracil-based chemotherapy for colorectal cancer. J Clin Oncol 2002; 20: 1491–8PubMedCrossRefGoogle Scholar
  31. 31.
    Jansman FG, Sleijfer DT, Coenen JL, et al. Risk factors determining chemotherapeutic toxicity in patients with advanced colorectal cancer. Drug Saf 2000; 23(4): 255–78PubMedCrossRefGoogle Scholar
  32. 32.
    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: 2282–92PubMedGoogle Scholar
  33. 33.
    Cunningham D, Coleman R. New options for outpatient chemotherapy: the role of oral fluoropyrimidines. Cancer Treat Rev 2001; 27(4): 211–20PubMedCrossRefGoogle Scholar
  34. 34.
    Pazdur R, Douillard JY, Skillings J, et al. Multicenter phase III study of 5-fluorouracil (5-FU) or UFTTM in combination with leucovorin (LV) in patients with metastatic colorectal cancer [abstract]. Proc Am Soc Clin Oncol 1999; 18: 263aGoogle Scholar
  35. 35.
    Hoff PM. Capecitabine as first-line treatment for metastatic colorectal cancer (CRC): integrated results of 1207 patients (pts) from 2 randomized, phase III studies [abstract]. Ann Oncol 2000; 11Suppl. 4: 60Google Scholar
  36. 36.
    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: 4097–106PubMedGoogle Scholar
  37. 37.
    Wellington K, Goa KL. Oral tegafur/uracil. Drugs Aging 2001; 18(12): 935–48PubMedCrossRefGoogle Scholar
  38. 38.
    Falcone A, Pfanner E, Ricci S, et al. Oral doxifluridine in elderly patients with metastatic colorectal cancer: a multicenter phase II study. Ann Oncol 1994; 5: 760–2PubMedGoogle Scholar
  39. 39.
    Carmichael J, Popiela T, Radstone D, et al. Randomized comparative study of Orzel (Oral Uracil/Tegafur (UFT) and leucovorin (LV)) versus parental 5-fluorouracil (5-FU) plus LV in patients with metastatic colorectal cancer [abstract]. Proc Am Soc Clin Oncol 1999; 18: 264aGoogle Scholar
  40. 40.
    Borner MM, Schöffski P, de Wit R, et al. Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial in advanced colorectal cancer. Eur J Cancer 2002; 38: 349–58PubMedCrossRefGoogle Scholar
  41. 41.
    Feliu J, Gonzalez-Baron M, Espinosa E, et al. Uracil and tegafur modulated with leucovorin: an effective regimen with low toxicity for the treatment of colorectal carcinoma in the elderly. Oncopaz Cooperative Group. Cancer 1997; 79: 1884–9PubMedCrossRefGoogle Scholar
  42. 42.
    Diaz-Rubio E, Sastre J, Abad A, et al. UFT plus or minus calcium folinate for metastatic colorectal cancer in older patients. Oncology 1999; 13: 35–40PubMedGoogle Scholar
  43. 43.
    Cassidy J, Twelves C, Van Cutsem E, et al. First-line oral capecitabine therapy in metastatic colorectal cancer: a favourable safety profile compared with intravenous 5-fluorouracil/leucovorin. Ann Oncol 2002; 13: 566–75PubMedCrossRefGoogle Scholar
  44. 44.
    Liu G, Franssen E, Fitch MI, et al. Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol 1997; 15: 110–5PubMedGoogle Scholar
  45. 45.
    Cunningham D, Zalcberg JR, Rath U, et al. Final results of a randomised trial comparing ‘Tomudex’ (raltitrexed) with 5-fluorouracil plus leucovorin in advanced colorectal cancer. Tomudex Colorectal Cancer Study Group. Ann Oncol 1996; 7: 961–5PubMedCrossRefGoogle Scholar
  46. 46.
    Pazdur R, Vincent M. Raltitrexed (Tomudex®) versus 5-fluorouracil plus leucovorin (5-FU + LV) in patients with advanced colorectal cancer (ACC): results of a randomized, multicenter, North American trial [abstract]. Proc Am Soc Clin Oncol 1997; 16: 228aGoogle Scholar
  47. 47.
    Cocconi G, Cunningham D, Van Cutsem E, et al. Open, randomized, multicenter trial of raltitrexed versus fluorouracil plus high-dose leucovorin in patients with advanced colorectal cancer. Tomudex Colorectal Cancer Study Group. J Clin Oncol 1998; 16: 2943–52PubMedGoogle Scholar
  48. 48.
    Maughan TS, James RD, Kerr DJ, et al. Comparison of survival palliation, and quality of life with three chemotherapy regimens in metastatic colorectal cancer: a multicentre randomised trial. Lancet 2002; 359: 1555–63PubMedCrossRefGoogle Scholar
  49. 49.
    Facchini T, Genet D, Berdah JF, et al. Raltitrexed (‘Tomudex’) has a manageable toxicity profile in elderly patients with metastatic colorectal cancer: final analysis of a multicentre study [abstract]. Proc Am Soc Clin Oncol 2000; 19: 298aGoogle Scholar
  50. 50.
    Mel J, Feliu J, Camps C, et al. ‘Tomudex’ (raltitrexed) in elderly patients with advanced colorectal cancer (ACC): an effective palliative treatment [abstract]. Proc Am Soc Clin Oncol 2000; 19: 257aGoogle Scholar
  51. 51.
    Cunningham D, Zalcberg J, Maroun J, et al. Efficacy, tolerability and management of raltitrexed (TomudexTM) monotherapy in patients with advanced colorectal cancer: a review of phase II/III trials. Eur J Cancer 2002; 38: 478–86PubMedCrossRefGoogle Scholar
  52. 52.
    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: 1041–7PubMedCrossRefGoogle Scholar
  53. 53.
    Van Cutsem E, Blijham GH. Irinotecan versus infusional 5-fluorouracil: a phase III study in metastatic colorectal cancer following failure on first-line 5-fluorouracil. V302 Study Group. Semin Oncol 1999; 26: 13–20PubMedGoogle Scholar
  54. 54.
    Miya T, Goya T, Fujii H, et al. Factors affecting the pharmacokinetics of CPT-11: the bodymass index, age and sex are independent predictors of pharmacokinetic parameters of CPT-11. Invest New Drugs 2001; 19: 61–7PubMedCrossRefGoogle Scholar
  55. 55.
    Rothenberg ML, Cox JV, De Vore FR, et al. A multicenter, phase II trial of weekly irinotecan (CP-T11) in patients with previously treated colorectal carcinoma. Cancer 1999; 85: 786–95PubMedCrossRefGoogle Scholar
  56. 56.
    Van Cutsem E, Dirix L, van Laethem J, et al. A randomized phase II trial of three different regimens of irinotecan (CPT-11): a fixed dose of 350 mg/m2 (A), or an individual dose optimisation (B), or a risk factor optimisation (C) in patients (pts) with metastatic colorectal cancer (MCRC) previously treated with 5-FU [abstract]. Proc Am Soc Clin Oncol 2000; 19: 244aGoogle Scholar
  57. 57.
    Sargent DJ, Niedzwiecki D, O’Connell MJ, et al. Recommendation for caution with irinotecan, fluorouracil, and leucovorin for colorectal cancer. N Engl J Med 2001; 345: 144–5PubMedCrossRefGoogle Scholar
  58. 58.
    Van Cutsem E, Douillard JY, Köhne CH. Toxicity of irinotecan in patients with colorectal cancer. N Engl J Med 2001; 345: 1351–2PubMedCrossRefGoogle Scholar
  59. 59.
    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: 2739–44PubMedGoogle Scholar
  60. 60.
    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: 214–9PubMedCrossRefGoogle Scholar
  61. 61.
    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: 2938–47PubMedGoogle Scholar
  62. 62.
    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: 136–47PubMedGoogle Scholar
  63. 63.
    Graham MA, Lockwood GF, Greenslade D, et al. Clinical pharmacokinetics of oxaliplatin: a critical review. Clin Cancer Res 2000; 6: 1205–18PubMedGoogle Scholar
  64. 64.
    Kouroussis C, Souglakos J, Kakolyris S, et al. Oxaliplatin in combination with infusional 5-fluorouracil and leucovorin every 2 weeks as first-line treatment in patients with advanced colorectal cancer: a phase II study. Oncology 2001; 61: 36–41PubMedCrossRefGoogle Scholar
  65. 65.
    Bollina R, Toniolo D, Belloni P, et al. Oxaliplatin (LOHP) and Irinotecan (CPT-11)-Oxiri-: phase I/II study in 5FU (F) refractory advanced colorectal cancer (ACRC) elderly patients (pts), a second line treatment [abstract]. Proc Am Soc Clin Oncol 2001; 20: 407aGoogle Scholar
  66. 66.
    Berlin JD. Targeting vascular endothelial growth factor in colorectal cancer. Oncology 2002; 16 (8 Suppl. 7): 13–5PubMedGoogle Scholar
  67. 67.
    O’dwyer PJ, Benson 3rd AB. Epidermal growth factor receptor-targeted therapy in colorectal cancer. Semin Oncol 2002; 29(14): 10–7PubMedCrossRefGoogle Scholar
  68. 68.
    Baselga J. Herceptin alone or in combination with chemotherapy in the treatment of HER2-positive metastatic breast cancer: pivotal trials. Oncology 2001; 61Suppl. 2: 14–21PubMedCrossRefGoogle Scholar
  69. 69.
    Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large B-cell lymphoma. N Engl J Med 2002; 364(4): 235–42CrossRefGoogle Scholar
  70. 70.
    Tebbutt NC, Cattell E, Midgley R, et al. Systemic treatment of colorectal cancer. Eur J Cancer 2002; 38(7): 1000–15PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2003

Authors and Affiliations

  • Friedemann Honecker
    • 1
  • Claus-Henning Köhne
    • 2
  • Carsten Bokemeyer
    • 1
  1. 1.Department of Hematology/Oncology/ImmunologyUniversity Medical Center II, Eberhard-Karls-UniversitätTübingenFederal Republic of Germany
  2. 2.Department of Hematology/Oncology/GastroenterologyUniversity Medical Center I, Universitätsklinikum Carl Gustav CarusDresdenFederal Republic of Germany

Personalised recommendations