Previous studies stating the combination of oxaliplatin and fluoropyrimidines as the standard of care for the adjuvant therapy of stage III colon cancer (CC) patients (pts) obtained non-convergent results and a reduced benefit for those over the age of 70 years.
We have assessed the impact of age (categorized as < or ≥ 70 years) on relapse free interval (RFI), defined as time from random to relapse or last disease assessment, in stage III CC pts randomized to receive 3 or 6 months of FOLFOX (FULV plus oxaliplatin) or CAPOX (capecitabine plus oxaliplatin) in the Italian, multicenter, phase III, TOSCA study (clinicaltrials.gov NCT0064660).
3,759 pts were enrolled from 130 sites. Overall, 2,360 of them had stage III disease, including 1,667 aged under 70 and 693 aged 70 or over. The elderly had an ECOG performance status (PS) more often equal to 1 (10.5% vs 3.3%, p <0.001), fewer women (40.8% vs 45.1, p=0.057), more T3/T4 tumors (90.9% vs 84.3%, p<0.001), a greater number of poorly differentiated (G3) tumors (28.3% vs 24.2%, p=0.039) and located on the right (40.9% vs 26.6%, p <0.001). No variation for type and treatment arm (p=0.965) was observed. The median follow-up was 62.5 and 60.6 months for the under 70 and the over 70, respectively. In pts over 70, we found a greater proportion of dose reductions (46.7% vs 41.4%, p=0.018), treatment interruptions (26.1% vs 19.3%, p<0.001) and a higher proportion of recurrences (24.2% vs 20.3%, p=0.033). The multivariable analysis of the RFI, corrected for sex, ECOG PS, tumor site, stage, grade, treatment, treatment duration and dose reduction, does not indicate a statistically significant effect of age (HR 1.19, 95% CI 0.98-1.44, p=0.082), although the point estimate is not negligible. Only a stage III high risk CC had a significant impact on RFI (HR [vs low risk] 2.05, 95% CI 1.71-2.46, p<0.001).
Comparing to younger pts, in elderly stage III CC pts treated with an oxaliplatin-based adjuvant therapy, a different treatment tolerability and a potential reduction of benefit was highlighted. Considerations should be made about the patient's general health status, his comorbidities and the management of the expected side effects.
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