Abstract

Abstract BACKGROUND AND AIMS Six-month adjuvant chemotherapy (CTH) is the current standard of care in locally advanced colorectal cancer (CRC). Recent studies have shown that shortening the treatment to 3 months results in moderately worse (0%–4% difference) overall survival. A longer duration of CTH may pose a risk of nephrotoxicity. We aimed to assess the effect of the duration of adjuvant CTH for CRC on kidney excretory function. METHOD We retrospectively studied medical records of 96 patients aged 38–83 (51% males) treated with adjuvant CTH for CRC. Patients underwent CTH either with regimens containing oxaliplatin and 5-fluorouracil/capecitabine (FOLFOX—31.3%; or XELOX—18.8%) or regimens containing 5-fluorouracil only (5-FU/LV; 50%). Glomerular filtration rate (calculated with the CKD-EPI formula) was analysed in three time points: before CTH, after 3 and 6 months of therapy. The deterioration of eGFR by 1.5 mL/min/1.73 m2 or more after 3 months and by 3 mL/min/1.73 m2 or more after 6 months was considered clinically significant. RESULTS We observed a clinically significant loss of eGFR after 3 months in 56.3% of patients. The risk of eGFR loss after 3 months was not related to gender, CTH regimen, clinical stage, initially low eGFR or comorbidities (P > 0.05). However, the clinically significant loss of eGFR was related to age (mean age 65.1 versus 61.3 years without eGFR loss; P = 0.03). Two-thirds (66.8%) of all patients were assessed in a 6-month time point. In this group, a significant eGFR loss was present in 42.4% of cases. Similarly, eGFR deterioration after 6 months was not related to proposed risk factors such as gender, CTH regimen type, clinical stage, low eGFR or comorbidities (P < 0.05), but was associated with age (mean age 66.3 versus 60.9 years without eGFR loss; P = 0.04). We observed a significant deterioration of eGFR more frequently in patients treated with 5-FU/LV regimens than with FOLFOX or XELOX (P = 0.03). However, patients, who underwent CTH with 5-FU/LV were older (P < 0.001), had lower initial eGFR (P = 0.02) and had hypertension more often (P = 0.03) than patients treated with oxaliplatin-containing regimens. In 92.9% of patients with significant eGFR loss after 6 months, we were able to observe rapid eGFR loss earlier, in a 3-month time point. However, one-third (31.6%) of patients with significant eGFR loss after 3 months did not present it after 6 months (P < 0.001). In patients with significant loss after 3 months, further deterioration after the next 3-month period occurred in 8 cases (21.1%), with a mean loss of 7.7 mL/min/1.73 m2. CONCLUSION Adjuvant CTH for CRC may cause a rapid loss of eGFR. The assessment of eGFR after 3 months of CTH is a predictor of further eGFR decline. Further investigation is needed to conclude if the shortage of CTH duration from 6 to 3 months may be beneficial for older patients in the context of nephrotoxicity.

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