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

Abstract

Purpose Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers. Methods In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive. Results A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49). Conclusion IDEA France, in which 90% of patients received mFOLFOX6, 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.

Efficacy of adjuvant cytokine-induced killer cell immunotherapy in patients with colorectal cancer after radical resection

“…Patients with T4 category have by far the worst survival rate regardless of stage II or III disease, 36 and adequate duration of adjuvant chemotherapy is recommended to these patients. 37,38 Consistent with previous observations, [36][37][38][39] our study also found that the 5-year OS rate of patients with T4 category or shorter chemotherapy duration was approximately 60%, whereas the 5-year OS rate of patients with T1-3 category or longer chemotherapy duration was approximately 80%. In the subgroup analyses, CIK cell immunotherapy was found to be significantly associated with an improved DFS and OS in patients with T4 category or shorter chemotherapy duration, but this association was absent in patients with T1-3 category or longer chemotherapy duration.…”

High symptom burden is associated with impaired quality of life in colorectal cancer patients during chemotherapy:A prospective longitudinal study

“…[18,19] The most common side effect from oxaliplatin is peripheral neuropathy, and the risk increases with cumulative doses. [18,19,[62][63][64] These symptoms can occur shortly after oxaliplatin administration and appear as symptoms such as numbness/tingling in the fingers, toes, or pharynx, and increased sensitivity to cold exposure. Neurotoxicity is a common dose-limiting toxicity of oxaliplatin.…”

Impact of relative dose intensity of FOLFOX adjuvant chemotherapy on risk of death among stage III colon cancer patients

“…Our ndings from population-based cancer registry data con rmed that higher chemotherapy RDI was needed in high-risk stage III colon cancers, compared with low-risk cancers, and are consistent with the conclusions from six randomized, phase 3 clinical trials conducted by the International Duration Evaluation of Adjuvant Therapy (IDEA) collaboration, which found that 6 months of FOLFOX particularly bene ted high-risk stage III colon cancers. These clinical trials evaluated whether 3 months of FOLFOX or CAPOX is non-inferior to 6 months of therapy in the rate of disease-free survival at 3 years [4,9,32,33]. Results from a pooled analysis of six trials showed that in stage III colon cancer patients treated with FOLFOX, 6-month therapy had a higher rate of disease-free survival than 3-month therapy, particularly in the high-risk group [9].…”

“…Results from a pooled analysis of six trials showed that in stage III colon cancer patients treated with FOLFOX, 6-month therapy had a higher rate of disease-free survival than 3-month therapy, particularly in the high-risk group [9]. Data from the IDEA France suggested that for FOLFOX6 regimen, patients with high-risk stage III colon cancer need 6-month chemotherapy for a maximal relapse risk reduction, for lowrisk cancer patients, the absolute difference in the 3-year disease free survival rate between 6 and 3 months of chemotherapy was clinically less relevant (2%) [33]. Older clinical trials have also shown that the e cacy of oxaliplatin is more signi cant in stage III N2 tumors, compared to stage III N1 tumors [34,35] (10-year overall survival advantage of 12.9% (p=0.013) in those with N2 tumors, and 6% (p=0.248) in those with N1 tumors, when adding oxaliplatin to 5-FU plus leucovorin [35]).…”