Advertisement

Chemotherapy in the Metastatic Setting

  • Gunnar FolprechtEmail author
Chapter

Abstract

Balancing between the competing risks of tumor death and toxicity with the influence of comorbidity and ageing on both, prognosis and treatment tolerability are essential for treatment decisions in elderly patients.

For patients enrolled in clinical trials, meta-analyses have shown an efficacy of chemotherapy in elderly patients similar to younger patients and no major differences in treatment effect. Nonrandomized phase II trials in elderly patients demonstrated similar results with chemotherapy as for younger patients. These analyses have therefore the methodological problem that the age distribution in clinical trials does not reflect daily clinical practice and that only a subset of elderly patients participated in the trials. The British FOCUS 2 enrolling frail patients demonstrated a better “overall treatment utility” if patients were treated with combination chemotherapy instead of fluoropyrimidine monotherapy.

Keywords

Metastatic colorectal cancer Elderly patients Chemotherapy 5-FU Fluoropyrimidine Oxaliplatin Irinotecan Comorbidity Stage IV metastases Palliative chemotherapy 

References

  1. 1.
    Van Cutsem E, Tabernero J, Lakomy R, et al. Intravenous (iv) aflibercept versus placebo in combination with irinotecan/5-fu (FOLFIRI) for second-line treatment of metastatic colorectal cancer (mCRC): results of a multinational phase III trial (EFC10262-VELOUR). Ann Oncol. 2011;22(5s; abstr O-0024).Google Scholar
  2. 2.
    Grothey A, Sobrero A, Siena S, et al. Results of a phase III randomized, double-blind, placebo-controlled, multicenter trial (CORRECT) of regorafenib plus best supportive care (BSC) versus placebo plus BSC in patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after standard therapies. J Clin Oncol. 2012; 30(suppl 4; abstr LBA385).Google Scholar
  3. 3.
    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(9):1330–8.PubMedCrossRefGoogle Scholar
  4. 4.
    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(9):1443–51.PubMedCrossRefGoogle Scholar
  5. 5.
    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(25):4085–91.PubMedCrossRefGoogle Scholar
  6. 6.
    Cassidy J, Twelves C, Van Cutsem E, et al. First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable safety profile compared with intravenous 5-fluorouracil/leucovorin. Ann Oncol. 2002;13(4):566–75.PubMedCrossRefGoogle Scholar
  7. 7.
    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(25):3457–65.PubMedCrossRefGoogle Scholar
  8. 8.
    Chau I, Norman AR, Cunningham D, et al. Elderly patients with fluoropyrimidine and thymidylate synthase inhibitor-resistant advanced colorectal cancer derive similar benefit without excessive toxicity when treated with irinotecan monotherapy. Br J Cancer. 2004;91(8):1453–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Seymour M. Sequential chemotherapy for colorectal cancer. Lancet Oncol. 2011;12(11):987–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Mitry E, Phelip F, Bonnetain F, et al. Phase III trial of chemotherapy with or without irinotecan in the front-line treatment of metastatic colorectal cancer in elderly patients (FFCD 2001–02 trial): results of a planned interim analysis. In: Proceedings of gastrointestinal cancer symposium (ASCO/AGA/ASTRO/SSO). 2008. Abstract 281.Google Scholar
  11. 11.
    Seymour MT, Maughan TS, Ledermann JA, et al. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. Lancet. 2007;370(9582):143–52.PubMedCrossRefGoogle Scholar
  12. 12.
    Ducreux M, Malka D, Mendiboure J, et al. Sequential versus combination chemotherapy for the treatment of advanced colorectal cancer (FFCD 2000–05): an open-label, randomised, phase 3 trial. Lancet Oncol. 2011;12(11):1032–44.PubMedCrossRefGoogle Scholar
  13. 13.
    Koopman M, Antonini NF, Douma J, et al. Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial. Lancet. 2007;370(9582):135–42.PubMedCrossRefGoogle Scholar
  14. 14.
    Sargent DJ, Kohne CH, Sanoff HK, et al. Pooled safety and efficacy analysis examining the effect of performance status on outcomes in nine first-line treatment trials using individual data from patients with metastatic colorectal cancer. J Clin Oncol. 2009;27(12):1948–55.PubMedCrossRefGoogle Scholar
  15. 15.
    Feliu J, Gonzalez BM, 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(10):1884–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Feliu J, Escudero P, Llosa F, et al. Capecitabine as first-line treatment for patients older than 70 years with metastatic colorectal cancer: an oncopaz cooperative group study. J Clin Oncol. 2005;23(13):3104–11.PubMedCrossRefGoogle Scholar
  17. 17.
    Mattioli R, Massacesi C, Recchia F, et al. High activity and reduced neurotoxicity of bi-­fractionated oxaliplatin plus 5-fluorouracil/leucovorin for elderly patients with advanced colorectal cancer. Ann Oncol. 2005;16(7):1147–51.PubMedCrossRefGoogle Scholar
  18. 18.
    Rosati G, Cordio S, Tucci A, et al. Phase II trial of oxaliplatin and tegafur/uracil and oral folinic acid for advanced or metastatic colorectal cancer in elderly patients. Oncology. 2005;69(2):122–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Rosati G, Cordio S, Bordonaro R, et al. Capecitabine in combination with oxaliplatin or irinotecan in elderly patients with advanced colorectal cancer: results of a randomized phase II study. Ann Oncol. 2010;21(4):781–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Comella P, Natale D, Farris A, et al. Capecitabine plus oxaliplatin for the first-line treatment of elderly patients with metastatic colorectal carcinoma: final results of the Southern Italy Cooperative Oncology Group Trial 0108. Cancer. 2005;104(2):282–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Feliu J, Salud A, Escudero P, et al. XELOX (capecitabine plus oxaliplatin) as first-line treatment for elderly patients over 70 years of age with advanced colorectal cancer. Br J Cancer. 2006;94(7):969–75.PubMedCrossRefGoogle Scholar
  22. 22.
    Benavides M, Pericay C, Valladares-Ayerbes M, et al. Oxaliplatin in combination with infusional 5-fluorouracil as first-line chemotherapy for elderly patients with metastatic colorectal cancer: a phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumors. Clin Colorectal Cancer. 2012;11:200–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Souglakos J, Pallis A, Kakolyris S, et al. Combination of irinotecan (CPT-11) plus 5-fluorouracil and leucovorin (FOLFIRI regimen) as first line treatment for elderly patients with metastatic colorectal cancer: a phase II trial. Oncology. 2005;69(5):384–90.PubMedCrossRefGoogle Scholar
  24. 24.
    Sastre J, Marcuello E, Masutti B, et al. Irinotecan in combination with fluorouracil in a 48-hour continuous infusion as first-line chemotherapy for elderly patients with metastatic colorectal cancer: a Spanish cooperative group for the treatment of digestive tumors study. J Clin Oncol. 2005;23(15):3545–51.PubMedCrossRefGoogle Scholar
  25. 25.
    Extermann M, Boler I, Reich RR, et al. Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. Cancer. 2012;118(13):3377–86.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2013

Authors and Affiliations

  1. 1.Medical Department I/University Cancer CenterUniversity Hospital Carl Gustav CarusDresdenGermany

Personalised recommendations