By Faith Reidenbach
NEW YORK (Reuters Health) – Capecitabine (Xeloda, Hoffman-La Roche), an oral prodrug of fluorouracil, deserves further investigation as a therapy for metastatic renal cell carcinoma that has failed immunotherapy, according to researchers in Austria.
Dr. Guenther G. Steger, of the University of Vienna, and colleagues note that in a previous study, renal carcinoma cell lines were shown to contain "a considerable amount" of thymidine phosphorylase. That is the key enzyme in the conversion of capecitabine to fluorouracil, they explain.
Prompted by this observation, and by favorable results from another group's study of capecitabine as a first-line agent for renal cell carcinoma, Dr. Steger's team conducted a single-institution phase II trial of second- and third-line capecitabine monotherapy. The 26 outpatients involved in the trial had metastatic renal cell carcinoma despite treatment with biological response modifiers and, in some cases, cytotoxic chemotherapy.
During a median followup period of 13 months, two patients (8.7%) achieved a partial response, the research team reports. Partial response was defined as at least a 50% reduction in lesion size with no new lesions.
Five patients (21.7%) showed a minor response (25% to 50% reduction in lesion size), 13 (56.5%) had stable disease, and in three (13.1%) the disease continued to progress. Three patients were lost to followup and were included only in the survival analysis.
The researchers calculated that 16 patients (70%) experienced a "clinical benefit response," which they defined as a partial response, minor response, or stable disease for at least six cycles. Overall, the median time to progression was 6 months, and the median survival time was 13 months.
Despite the extensive pretreatment of the patients, no WHO grade IV toxicity developed. Two patients had WHO grade III hand-foot syndrome, one had WHO grade III anemia, and 12 had one or more WHO grade II toxicities.
"Further clinical as well as in vitro research is needed to elucidate and–maybe–establish [capecitabine's] role to treat this disease," Dr. Steger told Reuters Health. Since the time the paper was published, he said, he and his group have "collected data on more patients and also of the combination of immunotherapy and capecitabine, but the data are too immature to publish right now."