Editor’s Note: This article was updated to include additional references to highlight the fact that conflicting results exist regarding the optimal duration of treatment.
Oxaliplatin-based adjuvant chemotherapy for 6 months led to superior outcomes compared with 3 months among patients with stage III colon cancer, according to a study published in the Journal of Clinical Oncology.1
Reducing the duration of chemotherapy without decreasing efficacy, and therefore the incidence of significant toxicities associated with treatment, is one of the primary goals of cancer management. Evidence from previous studies have shown that the legacy standard of 12-month fluoropyrimidine-based therapy could be reduced to 6 months, and perhaps even further to 3 months.
For the phase 3 International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France study (ClinicalTrials.gov Identifier: NCT00958738), researchers randomly assigned 2010 patients with advanced colon cancer to receive 3 months or 6 months of chemotherapy. Ninety-nine percent of patients had stage III colon cancer, of whom 75% and 25% had N1 and N2 disease, respectively, and 90% of patients received mFOLFOX6 and 10% were treated with CAPOX.
Overall, 94% of patients receiving treatment for 3 months and 78% of patients receiving treatment for 6 months completed treatment. There were 578 disease-free survival events; 314 in the 3-month arm and 264 in the 6-month arm.
After a median follow-up of 4.3 years, results showed that patients in the 3-month arm and 6-month arm had 3-year disease-free survival (DFS) rates of 72% and 76%, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05-1.46; P = .0112).
For patients who received mFOLFOX6, the 3-year DFS rate was 72% in the 3-month arm compared with 76.3% in the 6-month arm (HR, 1.27; 95% CI, 1.07-1.51). For patients with T4 and/or N2 disease the 3-year DFS rate was 58% and 66% respectively. For patients with T1-3N1 disease, the 3-year DFS rate was 81% and 83%, respectively.
The rates of maximal grade 2 or 3 neuropathy was 28% and 8%, respectively, among patients in the 3-month arm, and 41% and 25% in the 6-month arm (P < .001). The final rates of residual neuropathy that were worse than grade 1 was 3% and 7% in the 3- and 6-month arms, respectively.
The authors concluded that evidence from the study “shows superiority of 6 months of adjuvant chemotherapy compared with 3 months, especially in the T4 and/or N2 subgroups. These results should be considered alongside the international IDEA collaboration data.”
Despite the conclusions of this study, whether 3-month or 6-month adjuvant chemotherapy is superior to other remains a topic of controversy. Multiple studies2,3,4,5,6,7 have been performed among only to yield conflicting data, and future trials must be performed to solidify the standard duration of chemotherapy among patients with advanced colon cancer.
- Andre T, Vernerey D, Mineur L, et al. 3 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 [published online April 5, 2018]. J Clin Oncol. doi: 10.1200/JCO.2017.76.0355
- Ilson DH. Adjuvant therapy in colon cancer: less is more. Lancet Oncol. 2018;19(4):442-443. doi: 10.1016/S1470-2045(18)30127-X
- Iveson TJ, Kerr RS, Saunders MP, 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;19:562-578.
- Schilsky RL. A new IDEA in adjuvant chemotherapy for colon cancer. N Engl J Med. 2018;378;1242-1244. doi: 10.1056/NEJMe1800419
- Grothey A, Sobrero AF, Shields AF, et al. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 2018;378:1177-1188. doi: 10.1056/NEJMoa1713709
- 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 [published online April 5, 2018]. J Clin Oncol. doi: 10.1200/JCO.2017.76.2187
- Venook AP. Advances in adjuvant therapy for colon cancer: P value or practical value [published online April 5, 2018]. J Clin Oncol. doi: 10.1200/JCO.2018.77.8423