A retrospective observational study on the use of capecitabine in patients with severe renal impairment (GFR <30 mL/min) and end stage renal disease on hemodialysis.

Capecitabine (Xeloda) is an orally administered precursor of 5'deoxy-5-fluorouridine, which is a preferentially activated to 5-fluorouracil in tumors. It is used in the treatment of colorectal, gastric, and breast cancers. Based on a single Phase II trial, which included a total of 4 patients with severe renal impairment (GFR <30 mL/min), the manufacturer issued a 'Dear Doctor' letter contraindicating the use of capecitabine in these patients since a high rate of grade 3 and 4 adverse events were observed and because these patients tolerated shorter treatment durations.(1) We retrospectively studied 12 patients with a GFR <30 mL/min, including 2 patients with end stage renal disease on hemodialysis, who received capecitabine for mean duration of 7.1 months (1-26 months). The mean serum creatinine at the time of initiation of the drug was 2.63 mg/dL (1.8-6.4 mg/dL) and mean GFR was 20.9 mL/min (8-29 mL/min). Two patients remained on capecitabine after they progressed to end stage renal disease (ESRD) requiring hemodialysis (HD) for an additional 17 and 6 months, respectively. Most patients reported grade 1 and 2 adverse effects (AE), 2 patients reported grade 3 diarrhea and one patient died while on treatment with capecitabine. The starting dose ranged from 250 to 1000 mg/m(2), given twice daily at variable intervals. Dose modifications, with reductions of up to 50% of the starting dose, were made following reports of AEs. Serum tumor marker levels and/or follow up imaging studies were available on 9 patients. Response to capecitabine was documented in 4 patients, stable disease in 2, and disease progression in 3. We conclude that, with close monitoring of their clinical and chemical data, and with dose modification based on reported AEs, capecitabine can be safely administered to patients with severe renal impairment, including patients on hemodialysis.