Capecitabine is a novel fluoropyrimidine carbamate, orally administered and selectively activated to fluorouracil by a sequential triple enzyme pathway in liver and tumor cells.Oral capecitabine may be an active drug for the treatment of advanced renal cell carcinoma and is being evaluated in first- and second-line treatment schedules as monotherapy as well as in combination with immunotherapy agents.
In preclinical studies, renal cell tumors demonstrated high TP activity, suggesting that TP-activated capecitabine may be effective in this setting. In a pilot phase II study, capecitabine (1,250 mg/m2 twice daily for 14 days followed by a 7-day rest period) was administered to 22 patients with metastatic renal cell cancer that had progressed during or following immunotherapy. Among 12 patients for whom efficacy and toxicity data have been reported, one patient achieved a partial response, and disease was stabilized in all but one of the remaining patients (83%). There were no grade 4 adverse events and the only grade 3 adverse event was hand-foot syndrome, which occurred in two patients and resolved without capecitabine dose modification. Another phase II study has investigated capecitabine (1,000 mg/m2 twice daily on days 1-5 of weeks 5-8) in combination with immunotherapy (interleukin 2, interferon-, and oral 13-cis-retinoic acid) in 30 patients with metastatic renal cell carcinoma. This regimen, repeated for up to three cycles, produced an objective response rate of 34%, including two complete responses. A further 12 patients (40%) achieved disease stabilization. No grade 4 adverse events were observed, and grade 3 events were reported in only two patients (malaise and malaise, nausea/vomiting). There are published trials in combination with interferon, docetaxel and thalidomide.
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