Advertisement

The Optimal Duration of Adjuvant Therapy for Stage III Colon Cancer: the European Perspective

  • Giacomo Bregni
  • Sara Elena Rebuzzi
  • Alberto SobreroEmail author
Lower Gastrointestinal Cancers (AB Benson, Section Editor)
  • 81 Downloads
Part of the following topical collections:
  1. Topical Collection on Lower Gastrointestinal Cancers

Opinion statement

The International Duration Evaluation of Adjuvant Therapy (IDEA) collaboration was created to pool data from different studies worldwide in order to assess whether a shorter duration of adjuvant treatment in colon cancer could maintain the expected benefit while reducing toxicity. The results of the IDEA trials were clinically relevant. They confirmed a two- to sixfold reduction in neurotoxicity for the shorter duration across trials. Overall, the 3-year disease-free survival was very similar: only 0.9% lower for the 3 months group. However, the results were partially unexpected, because they revealed a difference among chemotherapy regimens (CAPOX better than FOLFOX) and risk groups within stage III. The similar outcome between 3 and 6 months of CAPOX coupled with the substantial reduction in toxicity makes us use the CAPOX regimen for 3 months for most stage III patients. An exception to this general rule is the patient with very high risk, i.e., either T4N1b-T4anyN2 or anyTN2b where we use 6 months of CAPOX. Our take from the trial results is also that FOLFOX should never be given for 3 months and preferably not used at all in the adjuvant setting. The conduction of the IDEA enterprise was truly global. The European contribution was major with three fourths of patients enrolled in the four European trials. Herein, we review the results of the “3 versus 6” trials and the literature regarding the interpretation of the collected data in Europe and in the rest of the world.

Keywords

Colon cancer Adjuvant chemotherapy IDEA trial Clinical trial interpretation 

Notes

Funding Information

Supported in part by grant AIRC 2018 (Associazione Italiana per la Ricerca sul Cancro)

Compliance with Ethical Standards

Conflict of Interest

The authors declare they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

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

  1. 1.
    André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350:2343–51.CrossRefGoogle Scholar
  2. 2.
    André T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009;27:3109–16.CrossRefGoogle Scholar
  3. 3.
    Kuebler JP, Wieand HS, O’Connell MJ, et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007;25:2198–204.CrossRefGoogle Scholar
  4. 4.
    André T, de Gramont A, Vernerey D, Chibaudel B, Bonnetain F, Tijeras-Raballand A, et al. Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol. 2015;33:4176–87.CrossRefGoogle Scholar
  5. 5.
    Yothers G, O’Connell MJ, Allegra CJ, et al. Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol. 2011;29:3768–74.CrossRefGoogle Scholar
  6. 6.
    Haller DG, Tabernero J, Maroun J, de Braud F, Price T, van Cutsem E, 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.CrossRefGoogle Scholar
  7. 7.
    Schmoll HJ, Tabernero J, Maroun J, de Braud F, Price T, van Cutsem E, et al. Capecitabine plus oxaliplatin compared with fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results of the NO16968 randomized controlled phase III trial. J Clin Oncol. 2015;33:3733–40.CrossRefGoogle Scholar
  8. 8.
    • Grothey A, Sobrero AF, Shields AF, et al. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 2018;378:1177–88 Prospective pooled analysis of six trials evaluating the noninferiority of 3 versus 6 months of adjuvant chemotherapy in colon cancer.CrossRefGoogle Scholar
  9. 9.
    Sobrero A, Lonardi S, Rosati G, et al. FOLFOX or CAPOX in stage II to III colon cancer: efficacy results of the Italian Three or Six Colon Adjuvant Trial. J Clin Oncol. 36:1478–1485.Google Scholar
  10. 10.
    Iveson TJ, Kerr RS, Saunders MP, Cassidy J, Hollander NH, Tabernero J, et al. 3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2018;19:562–78.CrossRefGoogle Scholar
  11. 11.
    André T, Vernerey D, Mineur L, Bennouna J, Desrame J, Faroux R, et al. Three versus 6 months of oxaliplatin-based adjuvant chemotherapy for patients with stage III colon cancer: disease-free survival results from a randomized, open-label, International Duration Evaluation of Adjuvant (IDEA) France, phase III trial. J Clin Oncol. 2018;36:1469–77.CrossRefGoogle Scholar
  12. 12.
    Souglakos J, Boukovinas I, Xynogalos S, et al. Three versus six months adjuvant oxaliplatin plus fluoropyrimidine chemotherapy for patients with stage III colon cancer: the Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant (IDEA) chemotherapy project. J Clin Oncol. 2018;36:83–93.CrossRefGoogle Scholar
  13. 13.
    Yoshino T, Yamanaka T, Kotaka M, et al. Efficacy of 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer (CC): results from phase III ACHIEVE trial as part of the International Duration Evaluation of Adjuvant therapy (IDEA) collaboration. Ann Oncol. 2017;28(Issue suppl_5,1).Google Scholar
  14. 14.
    • Naxerova K, Reiter JG, Brachtel E, et al. Origins of lymphatic and distant metastases in human colorectal cancer. Science. 2017;357:55–60 Archival tissue study showing the biological difference between stage II and stage III colon cancers.CrossRefGoogle Scholar
  15. 15.
    •• Sobrero A, Grothey A, Iveson T, et al. The hard road to data interpretation: 3 or 6 months of adjuvant chemotherapy for patients with stage III colon cancer? Ann Oncol. 2018;29:1099–107 Report of a special session at the Annual ESMO Meeting discussing the results of the IDEA trials and patients’ attitude.CrossRefGoogle Scholar
  16. 16.
    Ilson DH. Adjuvant therapy in colon cancer: less is more. Lancet Oncol. 2018;19:442–3.CrossRefGoogle Scholar
  17. 17.
    Schilsky RL. A new IDEA in adjuvant chemotherapy for colon cancer. N Engl J Med. 2018;378:1242–4.CrossRefGoogle Scholar
  18. 18.
    Haller DG, Cassidy J, Clarke SJ, Cunningham D, van Cutsem E, Hoff PM, et al. Potential regional differences for the tolerability profiles of fluoropyrimidines. J Clin Oncol. 2008;26:2118–23.CrossRefGoogle Scholar
  19. 19.
    Venook AP. Advances in adjuvant therapy for colon cancer: P value or practical value. J Clin Oncol. 2018;36:1461–2.CrossRefGoogle Scholar
  20. 20.
    Formica V, Zaniboni A, Loupakis F, Roselli M. Noninferiority of three months versus six months of oxaliplatin-based adjuvant chemotherapy for resected colon cancer. How should IDEA findings affect clinical practice? Int J Cancer. 2018;143:2342–50.CrossRefGoogle Scholar
  21. 21.
    Tang M, Price TJ, Shapiro J, Gibbs P, Haller DG, Arnold D, et al. Adjuvant therapy for resected colon cancer 2017, including the IDEA analysis. Expert Rev Anticancer Ther. 2018;18:339–49.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Giacomo Bregni
    • 1
  • Sara Elena Rebuzzi
    • 1
  • Alberto Sobrero
    • 1
    Email author
  1. 1.Policlinico San Martino IRCCSGenoaItaly

Personalised recommendations