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Current Trends in Systemic Therapies in Elderly Patients With Metastatic Colorectal Cancer

  • Systemic Therapies in Colorectal Cancer (SM Kazmi, Section Editor)
  • Published:
Current Colorectal Cancer Reports

Abstract

Purpose of Review

The incidence of colorectal cancer increases with age and the population is aging, making treatment of elderly patients with metastatic colorectal cancer (mCRC) an increasingly common part of oncology practice. We review the literature regarding systemic treatment of colorectal cancer in the elderly population.

Recent Findings

Most of the data for toxicity and efficacy of systemic therapies for mCRC in older patients comes from subgroup analysis of pooled phase II and III trials of both chemotherapy and targeted agents. These studies suggest that combination chemotherapy and targeted therapy are well-tolerated in fit elderly patients with slightly increased risk of toxicity.

Summary

Assessment of functional status independent of age can help differentiate which patients are candidates for combination chemotherapy, single-agent chemotherapy, targeted therapy, or supportive care. Fit, elderly patients should be treated as younger patients. Dose-reduced doublet therapy with dose escalation as tolerated is a safe and effective way to treat less-fit elderly patients. Most targeted therapies appear to be safe in the elderly population without significant concerns for increased toxicity.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Ries L, Melbert D, Krapcho M, et al. SEER cancer statistics review, 1975-2015. Bethesda: National Cancer Institute. http://seer.cancer.gov/csr/1975_2015/ (Accessed on February 21, 2019)

  2. Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29:3457–65. https://doi.org/10.1200/JCO.2011.34.7625.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. •• Mohile SG, Dale W, Somerfield MR, et al. Practical assessment and management of vulnerabilities in older patients received chemotherapy: ASCO guidelines for geriatric oncology. J Clin Oncol. 2018;36:2326–47. https://doi.org/10.1200/JCO.2018.78.8687 Guidelines for utilizing the geriatric assessment to identify vulnerabilities not typically captured with traditional oncology assessments.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Aparicio T, Jouve JL, Teillet L, Gargot D, Subtil F, le Brun-Ly V, 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. 2013;31:1464–70. https://doi.org/10.1200/JCO.2012.42.9894.

    Article  CAS  PubMed  Google Scholar 

  5. Sanoff HK, Goldberg RM, Pignone MP. A systematic review of the use of quality of life measure in colorectal cancer research with attention to outcomes in elderly patients. Clin Colorectal Cancer. 2007;6:700–9. https://doi.org/10.3816/CCC.2007.n.039.

    Article  PubMed  Google Scholar 

  6. Seymour MT, Thompson LC, Wasan HS, Middleton G, Brewster AE, Shepherd SF, et al. Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open label, randomized factorial trial. Lancet. 2011;377:1749–59. https://doi.org/10.1016/S0140-6736(11)60399-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Folprecht G, Cunningham D, Ross P, Glimelius B, di Costanzo F, Wils J, 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. https://doi.org/10.1093/annonc.mdh344.

    Article  CAS  PubMed  Google Scholar 

  8. Sargent DJ, Goldberg RM, Jacobson SD, Macdonald JS, Labianca R, Haller DG, et al. A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med. 2001;345:1091–7. https://doi.org/10.1056/NEJMoa010957.

    Article  CAS  PubMed  Google Scholar 

  9. Goldberg RM, Tabah-Fisch I, Bleiberg H, de Gramont A, Tournigand C, Andre T, 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. https://doi.org/10.1200/JCO.2006.06.9039.

    Article  CAS  PubMed  Google Scholar 

  10. Sastre J, Aranda E, Massutí B, Tabernero J, Chaves M, Abad A, et al. Elderly patients with advanced colorectal cancer derive similar benefit without excessive toxicity after first-line chemotherapy with oxaliplatin-based combinations: comparative outcomes from the 03-TTD-01 phase III study. Crit Rev Oncol Hematol. 2009;70:134–44. https://doi.org/10.1016/j.critrevonc.2008.11.002.

    Article  PubMed  Google Scholar 

  11. Arkenau HT, Graeven U, Kubicka S, Grothey A, Englisch-Fritz C, Kretzschmar A, et al. Oxaliplatin in combination with 5-fluorouracil/leucovorin or capecitabine in elderly patients with metastatic colorectal cancer. Clin Colorectal Cancer. 2008;7:60–4. https://doi.org/10.3816/CCC.2008.n.009.

    Article  CAS  PubMed  Google Scholar 

  12. Folprecht, 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. https://doi.org/10.1200/JCO.2007.14.0509.

    Article  CAS  PubMed  Google Scholar 

  13. Jackson NA, Barrueco J, Soufi-Mahjoubi R, Marshall J, Mitchell E, Zhang X, et al. Comparing safety and efficacy of first-line irinotecan/fluoropyrimidine combinations in elderly versus nonelderly patients with metastatic colorectal cancer: findings from the bolus, infusional, or capecitabine with camptostar-celecoxib study. Cancer. 2009;115:2617–29. https://doi.org/10.1002/cncr.24305.

    Article  CAS  PubMed  Google Scholar 

  14. Bullinger KL, Nardelli P, Wang Q, Rich MM. Oxaliplatin neurotoxicity of sensory transduction in rate proprioceptors. J Neurophysiol. 2011;106:704–9. https://doi.org/10.1152/jn.00083.2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. •• Kerckhove N, Collin A, Conde A, Chaleteix C, Pezet D, Balayssac D. Long-term effects, pathophysiological mechanisms, and risk factors or chemotherapy-induced peripheral neuropathies: a comprehensive literature review. Front Pharmacol. 2017;8:86. https://doi.org/10.3389/fphar.2017.00086 A comprehensive overview of the long-term effects of CIPN in cancer patients.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Tournigand C, André T, Achille E, Lledo G, Flesh M, Mery-Mignard D, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2004;22:229–37.

    Article  CAS  PubMed  Google Scholar 

  17. Saltz LB, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008;26:2013–9. https://doi.org/10.1200/JCO.2007.

    Article  CAS  Google Scholar 

  18. Scappaticci, et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst. 2007;15:1232–9. https://doi.org/10.1093/jnci/djm086.

    Article  Google Scholar 

  19. Meyerhardt JA, Li L, Sanoff HK, Carpenter W IV, Schrag D. Effectiveness of bevacizumab with first-line combination chemotherapy for Medicare patients with stage IV colorectal cancer. J Clin Oncol. 2012;30:608–15. https://doi.org/10.1200/JCO.2011.38.9650.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tsai HT, Marshall JL, Weiss SR, Huang CY, Warren JL, Freedman AN, et al. Bevacizumab use and risk of cardiovascular adverse events among elderly patients with colorectal cancer receiving chemotherapy: a population-based study. Ann Oncol. 2013;24:1574–9. https://doi.org/10.1093/annonc/mdt019.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Aparicio T, Bouché O, Taieb J, Maillard E, Kirscher S, Etienne PL, 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. 2018;29:133–8. https://doi.org/10.1093/annonc/mdx529.

    Article  CAS  PubMed  Google Scholar 

  22. Cunningham D, Lang I, Marcuello E, Lorusso V, Ocvirk J, Shin DB, 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. https://doi.org/10.1016/S1470-2045(13)70154-2.

    Article  CAS  PubMed  Google Scholar 

  23. Cutsem V, et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol. 2012;28:3499–506. https://doi.org/10.1200/JCO.2012.42.8201.

    Article  CAS  Google Scholar 

  24. Tabernero J, Yoshino T, Cohn AL, Obermannova R, Bodoky G, Garcia-Carbonero R, et al. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol. 2015;5:660–71. https://doi.org/10.1016/S1470-2045(15)70127-0.

    Article  CAS  Google Scholar 

  25. Bouchahda M, Macarulla T, Spano JP, et al. Cetuximab efficacy and safety in a retrospective cohort of elderly patients with heavily pretreated metastatic colorectal cancer. Crit Rev Oncol Hematol. 2008;67:255–62. https://doi.org/10.1016/j.clcc.2014.05.003.

    Article  CAS  PubMed  Google Scholar 

  26. Jehn CF, Böning L, Kröning H, Possinger K, Lüftner D. Cetuximab-based therapy in elderly comorbid patients with metastatic colorectal cancer. Br J Cancer. 2012;106:274–8. https://doi.org/10.1038/bjc.2011.554.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Sastre J, Grávalos 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. https://doi.org/10.1634/theoncologist.2011-0406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Van Cutsem E, Peeters M, Siena S, et al. 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. 2007;25:1658–64. https://doi.org/10.1200/JCO.2006.08.1620.

    Article  CAS  PubMed  Google Scholar 

  29. Pietrantonio F, Cremolini C, Aprile G, Lonardi S, Orlandi A, Mennitto A, et al. Single-agent panitumumab in frail elderly patients with advanced RAS and BRAF wild-type colorectal cancer: challenging drug label to light up new hope. Oncologist. 2015;20:1261–5. https://doi.org/10.1634/theoncologist.2015-0171.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lacouture ME, Mitchell EP, Piperdi B, Pillai MV, Shearer H, Iannotti N, et al. Skin toxicity evaluation protocol with panitumumab (STEPP), a phase II, open label, randomized trial evaluating the impact of a pre-emptive skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer. J Clin Oncol. 2010;28:1351–7. https://doi.org/10.1200/JCO.2008.21.7828.

    Article  CAS  PubMed  Google Scholar 

  31. •• Petrioli R, et al. Capecitabine plus oxaliplatin and bevacizumab, followed by maintenance treatment with capecitabine and bevacizumab for patients aged > 75 years with metastatic colorectal cancer. Clin Colorectal Cancer. 2018;17:663–9. https://doi.org/10.1016/j.clcc.2018.07.002 Study demonstrating both efficacy and safety of CAPOX-bevacizumab followed by maintenance Cap and Bev in patients aged > 75 years with metastatic colorectal cancer.

    Article  Google Scholar 

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Authors and Affiliations

  1. UNC Hospitals, Hematology/Oncology, Physicians Office Building, 170 Manning Drive, 3rd Floor, Chapel Hill, NC, 27599, USA

    Anna Griffith & Hanna Sanoff

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  1. Anna Griffith
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Correspondence to Anna Griffith.

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This article is part of the Topical Collection on Systemic Therapies in Colorectal Cancer

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Griffith, A., Sanoff, H. Current Trends in Systemic Therapies in Elderly Patients With Metastatic Colorectal Cancer. Curr Colorectal Cancer Rep 15, 105–111 (2019). https://doi.org/10.1007/s11888-019-00436-0

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