Skip to main content
SpringerLink
Log in

Targeted agents: review of toxicity in the elderly metastatic colorectal cancer patients

  • Review
  • Published:
Targeted Oncology Aims and scope Submit manuscript

Abstract

Colorectal cancer remains a major cause of cancer mortality in the Western world. With a median age at presentation of 71, patients with metastatic disease are often elderly with significant co-morbidities. In addition, elderly patients are more likely to be undertreated and under-represented in clinical trials. Therefore, as the available data from clinical trials are scarce, the optimal treatment strategy for this group of patients has not been adequately defined. In the setting of metastatic colorectal cancer, the introduction of so called targeted agents has significantly improved outcomes in the context of randomized clinical trials, while at the same time increasing treatment options for such patients. This review focuses on the role of targeted therapies in elderly patients with metastatic colorectal cancer, with specific reference to toxicity and tolerability. It should be noted that studies reviewed herein will have mostly included fit elderly patients fulfilling specific inclusion criteria. The available data so far are limited but suggest that targeted agents have similar efficacy and tolerability in elderly fit patients when compared with younger ones, provided caution is exercised in specific high-risk sub-groups. Clearly, further studies aimed at this specific patient population using well-established geriatric end-points will hopefully identify those patients more likely to benefit and less likely to suffer severe side effects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300

    Article  PubMed  Google Scholar 

  2. Aapro MS, Kohne CH, Cohen HJ, Extermann M (2005) Never too old? Age should not be a barrier to enrollment in cancer clinical trials. Oncologist 10:198–204

    Article  PubMed  Google Scholar 

  3. Berrino F, Capoccaccia R, Esteve J, Gatta G (1999) Survival of cancer patients in Europe: the EUROCARE-2 study. IARC Sci Publ 151:1–572

    Google Scholar 

  4. Hutchins LF, Unger JM, Crowley JJ et al (1999) Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 30:2061–2067

    Article  Google Scholar 

  5. Lewis JH, Kilgore ML, Goldman DP et al (2003) Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol 21(7):1383–1389

    Article  PubMed  Google Scholar 

  6. Folprecht G, Cunningham D, Ross P et al (2004) Efficacy of 5-fluorouracil-based chemotherapy in elderly patients with metastatic colorectal cancer: a pooled analysis of clinical trials. Ann Oncol 15(9):1330–1338

    Article  PubMed  CAS  Google Scholar 

  7. Popescu RA, Norman A, Ross PJ et al (1999) Adjuvant or palliative chemotherapy for colorectal cancer in patients 70 years or older. J Clin Oncol 17(8):2412–2418

    PubMed  CAS  Google Scholar 

  8. Folprecht G, Seymour MT, Saltz L et al (2008) 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 26(9):1443–1451

    Article  PubMed  CAS  Google Scholar 

  9. Goldberg RM, Tabah-Fisch I, Bleiberg H et al (2006) Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol 24(25):4085–4091

    Article  PubMed  CAS  Google Scholar 

  10. Figer A, Perez-Staub N, Carola E et al (2007) FOLFOX in patients aged between 76 and 80 years with metastatic colorectal cancer: an exploratory cohort of the OPTIMOX1 study. Cancer 110(12):2666–2671

    Article  PubMed  CAS  Google Scholar 

  11. François E, Berdah JF, Chamorey E et al (2008) Use of the folinic acid/5-fluorouracil/irinotecan (FOLFIRI) regimen in elderly patients as a first-line treatment for metastatic colorectal cancer: a Phase II study. Cancer Chemother Pharmacol 62:931–936

    Article  PubMed  Google Scholar 

  12. Aparicio T, Desramé J, Lecomte T et al (2003) Oxaliplatin- or irinotecan-based chemotherapy for metastatic colorectal cancer in the elderly. Br J Cancer 89:1439–1444

    Article  PubMed  CAS  Google Scholar 

  13. Cunningham D, Humblet Y, Siena S et al (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337–345

    Article  Google Scholar 

  14. Jonker DJ, O’Callaghan CJ, Karapetis CS et al (2009) Cetuximab for the treatment of colorectal cancer. N Engl J Med 360(14):1408–1417

    Article  Google Scholar 

  15. Asmis TR, Powell E, Karapetis CS et al (2011) Comorbidity, age and overall survival in cetuximab-treated patients with advanced colorectal cancer (ACRC)–results from NCIC CTG CO.17: a phase III trial of cetuximab versus best supportive care. Ann Oncol 22(1):118–126

    Article  PubMed  CAS  Google Scholar 

  16. Bouchahda M, Macarulla T, Spano JP et al (2008) Cetuximab efficacy and safety in a retrospective cohort of elderly patients with heavily pretreated metastatic colorectal cancer. Crit Rev Oncol Hematol 67(3):255–262

    Article  PubMed  CAS  Google Scholar 

  17. Fornaro L, Baldi GG, Masi G et al (2011) 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 78(3):243–251

    Article  PubMed  Google Scholar 

  18. Sastre J, Aranda E, Grávalos C et al (2011) 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 77(1):78–84

    Article  PubMed  CAS  Google Scholar 

  19. Van Cutsem E, Köhne C-H, Hitre E et al (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. NEJM 360:1408–1417

    Article  PubMed  Google Scholar 

  20. Su X, Lacouture ME, Jia Y, Wu S (2009) Risk of high-grade skin rash in cancer patients treated with cetuximab—an antibody against epidermal growth factor receptor: systemic review and meta-analysis. Oncology 77(2):124–133

    Article  PubMed  CAS  Google Scholar 

  21. Sobrero AF, Maurel J, Fehrenbacher L et al (2008) EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 26(14):2311–2319

    Article  PubMed  CAS  Google Scholar 

  22. Siena S, Glynne-Jones R, Adenis A et al (2010) Reduced incidence of infusion-related reactions in metastatic colorectal cancer during treatment with cetuximab plus irinotecan with combined corticosteroid and antihistamine premedication. Cancer 116(7):1827–1837

    Article  PubMed  CAS  Google Scholar 

  23. Tejpar S, Piessevaux H, Claes K et al (2007) Magnesium wasting associated with epidermal-growth-factor receptor-targeting antibodies in colorectal cancer: a prospective study. Lancet Oncol 8(5):387–394

    Article  PubMed  CAS  Google Scholar 

  24. Schrag D, Chung KY, Flombaum C, Saltz L (2005) Cetuximab therapy and symptomatic hypomagnesemia. J Natl Cancer Inst 97(16):1221–1224

    Article  PubMed  CAS  Google Scholar 

  25. Van Cutsem E, Peeters M, Siena S et al (2007) Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25(13):1658–1664

    Article  PubMed  Google Scholar 

  26. Van Cutsem E, Siena S, Humblet Y et al (2008) An open-label, single-arm study assessing safety and efficacy of panitumumab in patients with metastatic colorectal cancer refractory to standard chemotherapy. Ann Oncol 19(1):92–98

    Article  PubMed  Google Scholar 

  27. Douillard J-Y, Siena S, Cassidy J et al (2010) Randomized, phase III trial of panitumumab with infusional Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX4) Versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 31:4697–4705

    Article  Google Scholar 

  28. Peeters M, Price TJ, Cervantes A et al (2010) Randomized phase III study of panitumumab with Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol 31:4706–4713

    Article  Google Scholar 

  29. Heun J, Holen K (2007) Treatment with panitumumab after a severe infusion reaction to cetuximab in a patient with metastatic colorectal cancer: a case report. Clin Colorectal Cancer 6(7):529–531

    Article  PubMed  Google Scholar 

  30. Cartwright TH, Genther R (2008) Successful administration of panitumumab alone after severe infusion reaction to cetuximab in a patient with metastatic colorectal cancer. Clin Colorectal Cancer 7(3):202–203

    Article  PubMed  Google Scholar 

  31. Kabbinavar FF, Hurwitz HI, Yi J et al (2009) Addition of bevacizumab to fluorouracil-based first-line treatment of metastatic colorectal cancer: pooled analysis of cohorts of older patients from two randomized clinical trials. J Clin Oncol 27(2):199–205

    Article  PubMed  CAS  Google Scholar 

  32. Cassidy J, Saltz LB, Giantonio BJ et al (2010) Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies. J Cancer Res Clin Oncol 136(5):737–743

    Article  PubMed  CAS  Google Scholar 

  33. Kozloff M, Yood MU, Berlin J et al (2009) Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: the BRiTE observational cohort study. Oncologist 14(9):862–870

    Article  PubMed  CAS  Google Scholar 

  34. Kozloff MF, Berlin J, Flynn PJ et al (2010) Clinical outcomes in elderly patients with metastatic colorectal cancer receiving bevacizumab and chemotherapy: results from the BRiTE observational cohort study. Oncology 78(5–6):329–339

    Article  PubMed  CAS  Google Scholar 

  35. Van Cutsem E, Rivera F, Berry S et al (2009) Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 20(11):1842–1847

    Article  PubMed  Google Scholar 

  36. Kubala E, Bartos J, Petruzelka LB et al (2010) Safety and effectiveness of bevacizumab (bev) in combination with chemotherapy (CT) in elderly patients (pts) with metastatic colorectal cancer (mCRC): Results from a large Czech observational registry (CSTP). Proc Am Soc Clin Oncol Gastrointest Cancer Symp 2010, Abstr 467

  37. Nalluri SR, Chu D, Keresztes R et al (2008) Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA 300(19):2277–2285

    Article  PubMed  CAS  Google Scholar 

  38. Hurwitz HI, Saltz LB, Van Cutsem E et al (2011) Venous thromboembolic events with chemotherapy plus bevacizumab: a pooled analysis of patients in randomized phase II and III studies. J Clin Oncol 13:1757–1764

    Article  Google Scholar 

  39. Scappaticci FA, Skillings JR, Holden SN et al (2007) Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst 99(16):1232–1239

    Article  PubMed  Google Scholar 

  40. Ranpura V, Hapani S, Chuang J, Wu S (2010) Risk of cardiac ischemia and arterial thromboembolic events with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis of randomized controlled trials. Acta Oncol 49(3):287–297

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest statement

Although the authors have not received and will not receive benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this manuscript, benefits have been or will be received but are directed solely to a research fund, foundation, educational institution or other non-profit organization with which the authors are associated.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, B.O. Cyprus Oncology Center, 32 Acropoleos Ave., 2006, Strovolos, Nicosia, Cyprus

    Flora Kyriakou, Panteleimon Kountourakis & Demetris Papamichael

Authors
  1. Flora Kyriakou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Panteleimon Kountourakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Demetris Papamichael
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Demetris Papamichael.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kyriakou, F., Kountourakis, P. & Papamichael, D. Targeted agents: review of toxicity in the elderly metastatic colorectal cancer patients. Targ Oncol 6, 245–251 (2011). https://doi.org/10.1007/s11523-011-0198-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11523-011-0198-1

Keywords

Search

Navigation