Increased toxicity seen in women receiving adjuvant chemo for colon cancer

Female patients with colon cancer experience significantly greater toxicity with adjuvant chemotherapy compared with their male counterparts, a study has found.

The researchers used data from the ACCENT database to evaluate the influence of sex on the incidence and severity of major toxicities of fluoropyrimidine (5FU or capecitabine)-based adjuvant chemotherapy, with or without oxaliplatin, after curative surgery for colon cancer. They looked at each type of adjuvant chemotherapy (5FU, FOLFOX, capecitabine, CAPOX, and FOLFIRI).

The study population comprised 34,640 patients (median age, 61.0 years). Regardless of chemotherapy regimen, women were more likely to have a lower body mass index (BMI <18.5 kg/m², 4.5 percent vs 1.2 percent; 18.5–25 kg/m², 46.3 percent vs 39.4 percent), whereas men more often had a BMI of ≥25 kg/m² (59.3 percent vs 49.2 percent). Women more often had a performance score of 1 (20.8 percent vs 18.6 percent), whereas men were more likely to have a performance score of 0 (80.5 percent vs 78.5 percent).

Multivariable logistic regression analysis revealed that the following adverse events occurred with significantly greater frequency in women than in men: grade III/IV nausea (5FU: odds ratio [OR], 2.33; FOLFOX: OR, 2.34; p<0.001 for all), vomiting (5FU: OR, 2.38; FOLFOX: OR, 2.00; CAPOX: OR, 2.32; p<0.001 for all), diarrhoea (5FU: OR, 1.35; FOLFOX: OR, 1.60; FOLFIRI: OR, 1.57; p<0.001 for all), neutropenia (5FU: OR, 1.55; FOLFOX: OR, 1.96; FOLFIRI: OR, 2.01; capecitabine: OR, 4.07; p<0.001 for all), and leukopenia (5FU: OR, 1.74; FOLFIRI: OR, 1.75; p<0.001 for all). Women were consistently at increased risk of these toxicities.

The present data raise several important questions, including whether male patients with colon should receive higher doses of 5FU to enhance the effectiveness of adjuvant chemotherapy and whether the females should receive either reduced doses of 5FU or different and more intensive supportive treatments, according to the researchers. More trials are needed to investigate the surface area-based dosing of 5FU to optimize treatment.