Impact of Early Discontinuation of Oxaliplatin Treatment in Patients With Colon Cancer Receiving Adjuvant Chemotherapy

For patients with stage 5 colon cancer who received 6 months of oxaliplatin-based chemotherapy, early discontinuation of all treatment was associated with poorer oncologic outcomes. However, early discontinuation of solely oxaliplatin did not have a similar effect on outcomes.

Currently, oxaliplatin-based adjuvant chemotherapy for 6 months is the standard treatment for high-risk patients with stage 3 colon cancer. As Claire Gallois, MD, Georges Pompidou European Hospital, Paris, France, and coauthors wrote, “early treatment termination has been reported for about a third of patients,” adding, “oxaliplatin is also often stopped early because of cumulative peripheral sensory neurotoxicity.” This pooled analysis aimed to determine the prognostic impact of early discontinuation of all treatment, and early discontinuation of oxaliplatin while continuing fluorouracil and leucovorin/capecitabine within this patient population.

This study included data on patients with stage 3 colon cancer who were planned to receive 6 months of fluorouracil, leucovorin, and oxaliplatin or capecitabine plus oxaliplatin, retrieved from the ACCENT/IDEA databases. Early discontinuation of either treatment or oxaliplatin was defined as discontinuation only before a patient had received a maximum of 75% of the planned cycled. The analysis of early discontinuation of treatment included 10447 patients, 20.9% (n = 2184) of which had an early discontinuation of treatment. The analysis of early discontinuation of oxaliplatin included 7243 patients, 18.8% (n = 1359) of which experienced an early discontinuation of oxaliplatin. The reason for early termination was not recorded in the databases. All analyses were adjusted for established prognostic factors. The primary outcome was the association between early discontinuation of treatment or oxaliplatin and overall survival (OS), and disease-free survival (DFS).

There was a median follow-up duration of 78.8 months in the overall population. Early discontinuation of treatment was independently associated with a decrease in DFS (69% vs 78.8%; hazard ratio [HR]: 1.61; 95% confidence interval [CI], 1.48 to 1.75; P < .001) and overall survival (74.7% vs 84.7%, HR: 1.73; 95% CI, 1.54 to 1.98; P < .001), compared to those patients without any early discontinuation. There was not a similar decrease seen in either DFS (HR: 1.07; P = .3) or OS (HR: 1.13; P = .1) for those patients with an early discontinuation of oxaliplatin, compared to those patients without any early discontinuation. However, patients who received <50% of the planned oxaliplatin cycles had poorer outcomes than those who received 100% oxaliplatin cycles.

According to study authors, the study was limited due to a lack of information on the cause of discontinuation of treatments and on comorbid conditions which could influence DFS and OS. Additionally, patients who progressed on adjuvant chemotherapy were not included.

“These data favor discontinuing oxaliplatin while continuing fluoropyrimidine for patients with significant neurotoxicity who had received >50% of 6-month oxaliplatin,” Dr Gallois et al concluded.

Source:

Gallois C, Shi Q, Meyers JP, et al. Prognostic impact of early treatment and oxaliplatin discontinuation in patients with stage III colon cancer: an ACCENT/IDEA pooled analysis of 11 adjuvant trials. J Clin Oncol. Published online October 28, 2022. doi: 10.1200/JCO.21.02726