Colorectal Cancer in Older Adults: Systemic Treatments

  • Thomas Aparicio
Living reference work entry


Colorectal cancers are common in elderly patients. However, cancer screening is poorly used after 75. Elderly patients form a heterogeneous population with specific characteristics. Standards of care cannot therefore be transposed from young to elderly patients. Tumor resection is frequently performed, but adjuvant chemotherapy is rarely prescribed as there are no clearly established standards of care. In a metastatic setting, recent phase III studies have demonstrated that doublet frontline chemotherapy provided no survival benefit. Moreover, several studies have established the benefit of bevacizumab in association with chemotherapy. There is a lack of evidence for the efficacy of anti-epidermal growth factor antibodies in elderly patients. Geriatric assessments could help to select the adequate treatment strategy for individual patients. Geriatric oncology is now the challenge we have to face, and more specific trials are needed.


Radiotherapy Chemotherapy Targeted therapy Colorectal cancer Elderly 


  1. Andre T, Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350:2343–51.CrossRefPubMedGoogle Scholar
  2. Aparicio T, Desrame J, Lecomte T, et al. Oxaliplatin- or irinotecan-based chemotherapy for metastatic colorectal cancer in the elderly. Br J Cancer. 2003;89:1439–44.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Aparicio T, Navazesh A, Boutron I, et al. Half of elderly patients routinely treated for colorectal cancer receive a sub-standard treatment. Crit Rev Oncol Hematol. 2009;71:249–57.CrossRefPubMedGoogle Scholar
  4. Aparicio T, Jouve JL, Teillet L, et al. Geriatric factors predict chemotherapy feasibility: ancillary results of FFCD 2001-02 phase III study in first-line chemotherapy for metastatic colorectal cancer in elderly patients. J Clin Oncol. 2013a;31:1464–70.CrossRefPubMedGoogle Scholar
  5. Aparicio T, Schischmanoff O, Poupardin C, et al. Deficient mismatch repair phenotype is a prognostic factor for colorectal cancer in elderly patients. Dig Liver Dis. 2013b;45:245–50.CrossRefPubMedGoogle Scholar
  6. Aparicio T, Schischmanoff O, Poupardin C, et al. High prevalence of deficient mismatch repair phenotype and the V600E BRAF mutation in elderly patients with colorectal cancer. J Geriatr Oncol. 2014;5:384–8.CrossRefPubMedGoogle Scholar
  7. Aparicio T, Francois E, Cristol-Dalstein L, et al. PRODIGE 34 – FFCD 1402 – ADAGE: adjuvant chemotherapy in elderly patients with resected stage III colon cancer. A randomized phase 3 trial. Dig Liver Dis. 2016a;48:206–7.CrossRefPubMedGoogle Scholar
  8. Aparicio T, Lavau-Denes S, Phelip JM, et al. Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001-02). Ann Oncol. 2016b;27:121–7.CrossRefPubMedGoogle Scholar
  9. Aparicio T, Pamoukdjian F, Quero L, et al. Colorectal cancer care in elderly patients: unsolved issues. Dig Liver Dis. 2016c;48:1112–8.CrossRefPubMedGoogle Scholar
  10. Aparicio T, Gargot D, Teillet L et al. Geriatric factors analyses from FFCD 2001-02 phase III study of first-line chemotherapy for elderly metastatic colorectal cancer patients. Eur J Cancer. 2017;74:98–108.Google Scholar
  11. Aparicio T, Bouché O, Taieb J et al. Bevacizumab + chemotherapy versus chemotherapy alone in elderly patients with untreated metastatic colorectal cancer: a randomized phase II trial - PRODIGE 20 study results. Ann Oncol. 2018a;29(1):133–138.Google Scholar
  12. Aparicio T, Bouché O, Francois E et al. Geriatric analysis from PRODIGE 20 randomized phase II trial evaluating bevacizumab + chemotherapy versus chemotherapy alone in older patients with untreated metastatic colorectal cancer. Eur J Cancer. 2018b (in press).Google Scholar
  13. Bellera CA, Rainfray M, Mathoulin-Pelissier S, et al. Screening older cancer patients: first evaluation of the G-8 geriatric screening tool. Ann Oncol. 2012;23:2166–72.CrossRefPubMedGoogle Scholar
  14. Bouvier AM, Launoy G, Lepage C, et al. Trends in the management and survival of digestive tract cancers among patients aged over 80 years. Aliment Pharmacol Ther. 2005;22:233–41.CrossRefPubMedGoogle Scholar
  15. Cassidy J, Saltz LB, Giantonio BJ, et al. Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies. J Cancer Res Clin Oncol. 2010;136:737–43.CrossRefPubMedGoogle Scholar
  16. Cunningham D, Lang I, Marcuello E, et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol. 2013;14:1077–85.CrossRefPubMedGoogle Scholar
  17. van den Broek CB, Bastiaannet E, Dekker JW. Time trends in chemotherapy (administration and costs) and relative survival in stage III colon cancer patients – a large population-based study from 1990 to 2008. Acta Oncol. 2013;52:941–9.CrossRefPubMedGoogle Scholar
  18. Doat S, Thiebaut A, Samson S, et al. Elderly patients with colorectal cancer: treatment modalities and survival in France. National data from the ThInDiT cohort study. Eur J Cancer. 2014;50:1276–83.CrossRefPubMedGoogle Scholar
  19. Douillard J, Siena S, Peeters M, et al. Impact of baseline age on efficacy and safety of first-line panitumumab (pmab) + FOLFOX4 vs FOLFOX4 treatment. Ann Oncol. 2014;25(Suppl 4):547P.Google Scholar
  20. van Erning FN, Janssen-Heijnen ML, Creemers GJ, et al. Recurrence-free and overall survival among elderly stage III colon cancer patients treated with CAPOX or capecitabine monotherapy. Int J Cancer. 2017;140:224–33.CrossRefPubMedGoogle Scholar
  21. Extermann M, Boler I, Reich RR. Predicting the risk of chemotherapy toxicity in older patients: the chemotherapy risk assessment scale for high-age patients (CRASH) score. Cancer. 2012;118:3377–86.CrossRefPubMedGoogle Scholar
  22. Faivre-Finn C, Bouvier AM, Mitry E, et al. Chemotherapy for colon cancer in a well-defined French population: is it under- or over-prescribed? Aliment Pharmacol Ther. 2002;16:353–9.CrossRefPubMedGoogle Scholar
  23. Ferlay J, Teliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49:1374–403.CrossRefPubMedGoogle Scholar
  24. Folprecht G, Cunningham D, Ross P, et al. Efficacy of 5-fluorouracil-based chemotherapy in elderly patients with metastatic colorectal cancer: a pooled analysis of clinical trials. Ann Oncol. 2004;15:1330–8.CrossRefPubMedGoogle Scholar
  25. Folprecht G, Seymour MT, Saltz L, et al. Irinotecan/fluorouracil combination in first-line therapy of older and younger patients with metastatic colorectal cancer: combined analysis of 2,691 patients in randomized controlled trials. J Clin Oncol. 2008;26:1443–51.CrossRefPubMedGoogle Scholar
  26. Folprecht G, Köhne C, Bokemeyer C, et al. Cetuximab and 1st-line chemotherapy in elderly and younger patients with metastatic colorectal cancer: a pooled analysis of the CRISTAL and OPUS studies. Ann Oncol [Eur Cancer Congr]. 2010;21(Suppl. 8):A597.Google Scholar
  27. Fornaro L, Baldi GG, Masi G, et al. Cetuximab plus irinotecan after irinotecan failure in elderly metastatic colorectal cancer patients: clinical outcome according to KRAS and BRAF mutational status. Crit Rev Oncol Hematol. 2011;78:243–51.CrossRefPubMedGoogle Scholar
  28. Francois E, Berdah JF, Chamorey E, et al. Use of the folinic acid/5-fluorouracil/irinotecan (FOLFIRI 1) regimen in elderly patients as a first-line treatment for metastatic colorectal cancer: a phase II study. Cancer Chemother Pharmacol. 2008;62:931–6.CrossRefPubMedGoogle Scholar
  29. Frerot M, Jooste V, Binquet C, et al. Factors influencing inclusion in digestive cancer clinical trials: a population-based study. Dig Liver Dis. 2015;47:891–6.CrossRefPubMedGoogle Scholar
  30. Goldberg RM, Tabah-Fisch I, Bleiberg H, et al. Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol. 2006;24:4085–91.CrossRefPubMedGoogle Scholar
  31. Haller D, Tabernero J, Maroun J, et al. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol. 2011;29:1465–71.CrossRefPubMedGoogle Scholar
  32. Hamaker ME, Jonker JM, de Rooij SE, et al. Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients with cancer: a systematic review. Lancet Oncol. 2012;13:e437–44.CrossRefPubMedGoogle Scholar
  33. Hurria A, Togawa K, Mohile SG, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29:3457–65.CrossRefPubMedPubMedCentralGoogle Scholar
  34. Jehn CF, Boning L, Kroning H, et al. Influence of comorbidity, age and performance status on treatment efficacy and safety of cetuximab plus irinotecan in irinotecan-refractory elderly patients with metastatic colorectal cancer. Eur J Cancer. 2014;50:1269–75.CrossRefPubMedGoogle Scholar
  35. Jung B, Pahlman L, Johansson R, et al. Rectal cancer treatment and outcome in the elderly: an audit based on the Swedish rectal cancer registry 1995–2004. BMC Cancer. 2009;9:68.CrossRefPubMedPubMedCentralGoogle Scholar
  36. Köhne C, 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;13:308–17.CrossRefPubMedGoogle Scholar
  37. Kozloff M, Yood MU, Berlin J, et al. Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: the BRiTE observational cohort study. Oncologist. 2009;14:862–70.CrossRefPubMedGoogle Scholar
  38. Landre T, Uzzan B, Nicolas P, et al. Doublet chemotherapy vs. single-agent therapy with 5FU in elderly patients with metastatic colorectal cancer. A meta-analysis. Int J Color Dis. 2015;30:1305–10.CrossRefGoogle Scholar
  39. Laurent M, Des Guetz G, Bastuji-Garin S et al. Chronological Age and Risk of Chemotherapy Nonfeasibility: A Real-Life Cohort Study of 153 Stage II or III Colorectal Cancer Patients Given Adjuvant-modified FOLFOX6. Am J Clin Oncol. 2018;41(1):73–80.Google Scholar
  40. Lievre A, Laurent V, Cudennec T, et al. Management of patients over 80 years of age treated with resection for localised colon cancer: results from a French referral centre. Dig Liver Dis. 2014;46:838–45.CrossRefPubMedGoogle Scholar
  41. Liuu E, Canoui-Poitrine F, Tournigand C, et al. Accuracy of the G-8 geriatric-oncology screening tool for identifying vulnerable elderly patients with cancer according to tumour site: the ELCAPA-02 study. J Geriatr Oncol. 2014;5:11–9.CrossRefPubMedGoogle Scholar
  42. Maas M, Beets-Tan RG, Lambregts DM, et al. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol. 2011;29:4633–40.CrossRefPubMedGoogle Scholar
  43. Mahoney T, Kuo YH, Topilow A, et al. Stage III colon cancers: why adjuvant chemotherapy is not offered to elderly patients. Arch Surg. 2000;135:182–5.CrossRefPubMedGoogle Scholar
  44. Manceau G, Karoui M, Werner A, et al. Comparative outcomes of rectal cancer surgery between elderly and non-elderly patients: a systematic review. Lancet Oncol. 2012;13:e525–36.CrossRefPubMedGoogle Scholar
  45. Martijn H, Vulto JC. Should radiotherapy be avoided or delivered differently in elderly patients with rectal cancer? Eur J Cancer. 2007;43:2301–6.CrossRefPubMedGoogle Scholar
  46. McCleary NJ, Meyerhardt JA, Green E, et al. Impact of age on the efficacy of newer adjuvant therapies in patients with stage II/III colon cancer: findings from the ACCENT database. J Clin Oncol. 2013;31:2600–6.CrossRefPubMedPubMedCentralGoogle Scholar
  47. O’Connor ES, Greenblatt DY, LoConte NK, et al. Adjuvant chemotherapy for stage II colon cancer with poor prognostic features. J Clin Oncol. 2011;29:3381–8.CrossRefPubMedPubMedCentralGoogle Scholar
  48. Olsson LI, Granstrom F, Glimelius B. Socioeconomic inequalities in the use of radiotherapy for rectal cancer: a nationwide study. Eur J Cancer. 2011;47:347–53.CrossRefPubMedGoogle Scholar
  49. Paillaud E, Liuu E, Laurent M, et al. Geriatric syndromes increased the nutritional risk in elderly cancer patients independently from tumour site and metastatic status. The ELCAPA-05 cohort study. Clin Nutr. 2014;33:330–5.CrossRefPubMedGoogle Scholar
  50. Papamichael D, Audisio RA, Glimelius B, et al. Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013. Ann Oncol. 2015;26:463–76.CrossRefPubMedGoogle Scholar
  51. Price TJ, Zannino D, Wilson K, et al. Bevacizumab is equally effective and no more toxic in elderly patients with advanced colorectal cancer: a subgroup analysis from the AGITG MAX trial: an international randomised controlled trial of Capecitabine, Bevacizumab and Mitomycin C. Ann Oncol. 2012;23:1531–6.CrossRefPubMedGoogle Scholar
  52. Quarini C, Gosney M. Review of the evidence for a colorectal cancer screening programme in elderly people. Age Ageing. 2009;38:503–8.CrossRefPubMedGoogle Scholar
  53. Quasar Collaborative Group, Gray R, Barnwell J, McConkey C, et al. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet. 2007;370:2020–9.CrossRefGoogle Scholar
  54. Ribic CM, Sargent DJ, Moore MJ, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med. 2003;349:247–57.CrossRefPubMedPubMedCentralGoogle Scholar
  55. Rosati G, Aprile G, Cardellino GG, et al. A review and assessment of currently available data of the EGFR antibodies in elderly patients with metastatic colorectal cancer. J Geriatr Oncol. 2016;7:134–41.CrossRefPubMedGoogle Scholar
  56. 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;345:1091–7.CrossRefPubMedGoogle Scholar
  57. Sargent DJ, Marsoni S, Monges G, et al. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol. 2010;28:3219–26.CrossRefPubMedPubMedCentralGoogle Scholar
  58. Sastre J, Aranda E, Gravalos C, et al. First-line single-agent cetuximab in elderly patients with metastatic colorectal cancer. A phase II clinical and molecular study of the Spanish group for digestive tumor therapy (TTD). Crit Rev Oncol Hematol. 2011;77:78–84.CrossRefPubMedGoogle Scholar
  59. Sastre J, Gravalos C, Rivera F, et al. First-line cetuximab plus capecitabine in elderly patients with advanced colorectal cancer: clinical outcome and subgroup analysis according to KRAS status from a Spanish TTD group study. Oncologist. 2012;17:339–45.CrossRefPubMedPubMedCentralGoogle Scholar
  60. Sastre J, Massuti B, Pulido G, et al. First-line single-agent panitumumab in frail elderly patients with wild-type KRAS metastatic colorectal cancer and poor prognostic factors: a phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours. Eur J Cancer. 2015;51:1371–80.CrossRefPubMedGoogle Scholar
  61. Seymour MT, Thompson LC, Wasan HS, et al. Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial. Lancet. 2011;377:1749–59.CrossRefPubMedPubMedCentralGoogle Scholar
  62. Shankaran V, Mummy D, Koepl L, et al. Adverse events associated with bevacizumab and chemotherapy in older patients with metastatic colorectal cancer. Clin Colorectal Cancer. 2013;12:204–213.e1.CrossRefPubMedGoogle Scholar
  63. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. Cancer J Clin. 2016;66:7–30.CrossRefGoogle Scholar
  64. Sorbye H, Pfeiffer P, Cavalli-Bjorkman N, et al. Clinical trial enrollment, patient characteristics, and survival differences in prospectively registered metastatic colorectal cancer patients. Cancer. 2009;115:4679–87.CrossRefPubMedGoogle Scholar
  65. Soubeyran P, Fonck M, Blanc-Bisson C, et al. Predictors of early death risk in older patients treated with first-line chemotherapy for cancer. J Clin Oncol. 2012;30:1829–34.CrossRefPubMedGoogle Scholar
  66. Spitzer WO, Dobson AJ, Hall J, et al. Measuring the quality of life of cancer patients: a concise QL-index for use by physicians. J Chronic Dis. 1981;34:585–97.CrossRefPubMedGoogle Scholar
  67. Tournigand C, Andre T, Bonnetain F, et al. Adjuvant therapy with fluorouracil and oxaliplatin in stage II and elderly patients (between ages 70 and 75 years) with colon cancer: subgroup analyses of the Multicenter International Study of Oxaliplatin, Fluorouracil, and Leucovorin in the Adjuvant Treatment of Colon Cancer trial. J Clin Oncol. 2012;30:3353–60.CrossRefPubMedGoogle Scholar
  68. Van Cutsem E, Peeters M, Siena S, et al. A phase III randomized controlled trial of panitumumab (Pmab) in patients (pts) with metastatic colorectal cancer (mCRC): subset analyses in elderly pts and in pts with poor performance status. Proceedings of ASCO GI Cancer Symposium. J Clin Oncol. San Francisco, A349. 2007.Google Scholar
  69. Van Cutsem E, Sobrero A, Siena S, et al. Regorafenib in progressive metastatic colorectal cancer: analysis of age subgroups in the phase III CORRECT trial. J Clin Oncol. 2013;31(suppl):A3636.Google Scholar
  70. Yee KW, Pater JL, Pho L, et al. Enrollment of older patients in cancer treatment trials in Canada: why is age a barrier? J Clin Oncol. 2003;21:1618–23.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Gastroenterology and Digestive Oncology DepartmentSaint Louis Hospital, APHP/ René Diderot University, Sorbonne Paris CitéParisFrance

Section editors and affiliations

  • Etienne Brain
    • 1
  1. 1.Department of Medical Oncology, Institute CurieHôpital René HugueninSaint-CloudFrance

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