The Optimal Duration of Adjuvant Therapy for Stage III Colon Cancer: the European Perspective
- 81 Downloads
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.
KeywordsColon cancer Adjuvant chemotherapy IDEA trial Clinical trial interpretation
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
- 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
- 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
- 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.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.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.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.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
- 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