Expression of thymidine phosphorylase in peripheral blood cells of breast cancer patients is not increased by paclitaxel

A total of 128 consecutive blood samples were collected from eight patients with advanced breast cancer receiving paclitaxel weekly at a dose of 80 mg/m2. To assess the expression of TP in blood cells, samples were collected prior to first therapy, at the end of infusion, and up to 15 days thereafter. This procedure was repeated during the sixth application of paclitaxel. After isolation of the peripheral mononuclear blood cells, the expression of TP was assessed by ELISA. In parallel, paclitaxel level in plasma was evaluated at three selected time points as pharmacokinetic control parameter.Paclitaxel concentrations at the end of infusion did not change significantly from week 1 to week 6. The expression of TP in peripheral mononuclear blood cells decreased significantly after infusion below pretherapeutic values (p = 0.023; n = 8). After the nadir on day 3, the expression of TP increased moderately returning to baseline levels within one week. The overall picture in week 6 was similar to week 1. Using a trend analysis, neither a short-term nor a long-term induction of TP was observed.TP in peripheral mononuclear blood cells was hardly regulated under therapy with paclitaxel. Therefore, no increased haematotoxicity due to TP upregulation is expected from the combination of taxanes and capecitabine.In advanced breast cancer, combinations of cytotoxic agents with synergistic antitumour effect deserve particular attention. Different groups reported increased response rates and prolonged time to disease progression in combination therapy as compared to single-agent treatment. Yet, combining cytotoxic drugs is usually associated with increased toxicity. A synergistic effect has been hypothesized for paclitaxel and capecitabine, a prodrug of 5-fluorouracil. Taxanes are a group of compounds that interact with the β subunit of tubulin and induce tubulin polymerization thus interfering with the normal balance between polymerization and its contrary, depolymerisation. This m