Treatment Adherence, Toxicity, and Outcomes With Adjuvant Fluoropyrimidine Plus Oxaliplatin in Early-Onset Colorectal Cancer

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In an analysis of data from the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) database reported in the Journal of Clinical Oncology, Fontana et al found a greater risk of relapse and cancer-specific mortality after adjuvant fluoropyrimidine/oxaliplatin chemotherapy in patients with early-onset vs later-onset colorectal cancer, despite better treatment adherence in younger patients.

The study involved data on individual patients with stage II or III colorectal cancer from six trials in the IDEA database assessing 3 or 6 months of adjuvant fluoropyrimidine/oxaliplatin chemotherapy. Early-onset colorectal cancer was defined as onset at age < 50 years, and late-onset colorectal cancer, as onset at ≥ 50 years.

Key Findings

Among the 16,349 patients, 1,564 (9.6%) had early-onset disease.

Compared with patients who had late-onset colorectal cancer, the early-onset group had a better Eastern Cooperative Oncology Group performance status (0 in 86% vs 80%, P < .01), similar T stage (T1–3/T4 in 76%/24% vs 77%/23%, P = .97), and higher incidence of N2 disease (24% vs 22%, P < .01) and were more likely to complete the planned treatment duration (83.2% vs 78.2 %, P < .01) and to receive a higher treatment dose intensity, particularly among those receiving 6-month regimens.

Grade ≥ 3 adverse events occurred in 36% of the early-onset group and 39% of the late-onset group. Gastrointestinal toxicity was more common in early-onset patients (any grade in 68.7% vs 64.6%, P = .044), with significant differences observed for vomiting and nausea (both P < .0001). Hematologic toxicity was more common in late-onset patients (any grade in 69.4% vs 62.2%, P = .0002), with significant differences in febrile neutropenia (P = .012), neutropenia (P = .002), and thrombocytopenia (P < .0001).

No significant difference in 3-year disease-free survival was observed between early-onset vs late-onset colorectal cancer (76% vs 78%, hazard ratio [HR] = 1.01, 95% confidence interval [CI] =, 0.91–1.13, P = .81) among all patients or in stage II and III subgroups.

Relapse-free survival at 3 years was significantly poorer in early-onset disease overall (75% vs 79%, HR = 1.13, 95% CI = 1.01–1.27, P = .04) and in stage III disease (69% vs 76%, HR = 1.21, 95% CI = 1.07–1.37, P = .003) and high-risk stage III disease (54% vs 65%, HR = 1.33, 95% CI = 1.14–1.55, P < .001).

Overall survival at 5-years was higher in the early-onset group (86% vs 83%, HR = 0.84, 95% CI = 0.73–0.97, P = 0.02). However, 5-year cancer-specific mortality was greater in stage III early-onset disease (15% vs 12%, HR = 1.20, 95% CI = 1.02–1.42, P = .03) and in high-risk stage III disease (24% vs 20%, HR = 1.21, 95% CI = 1.00–1.47, P < .06). 

The investigators concluded: “Young age is negatively prognostic in high-risk stage III [colorectal cancer] and associated with significantly higher relapse rate; this is despite better treatment adherence and higher administered treatment intensity, suggesting more aggressive disease biology.”

Elisa Fontana, MD, PhD, of the Sarah Cannon Research Institute UK, London, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the European Organisation for Research and Treatment of Cancer, Japanese Foundation for Multidisciplinary Treatment of Cancer, National Cancer Institute, and others. For full disclosures of the study authors, visit

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