Metronomic administration of zoledronic acid and taxotere combination in castration resistant prostate cancer patients : phase I ZANTE trial

BACKGROUND: Docetaxel (DTX) and zoledronic acid (ZOL) are effective in patients with hormone resistant prostate cancer (HRPC) with bone metastases. A phase I clinical trial of metronomic administration of Zoledronic Acid AN d TaxoterE combination (ZANTE trial) in 2 different sequences was conducted in HRPC. RESULTS: The maximum tolerated dose was not achieved with sequence A. Two patients at third level of sequence B developed dose limiting toxicity. A disease control was obtained in six out of nine patients treated with sequence A, where a decrease of biological markers and PSA were also observed. No evidence of anti-tumor activity was observed in patients treated with sequence B. PATIENTS AND METHODS: Twenty-two patients enrolled into the study (median age: 73 years; range: 43-80) received one of three escalated doses of DTX (30, 40 and 50 mg/m(2)) in combination with a fixed dose of ZOL (2 mg), both administered every 14 days in two different sequences: DTX at the day 1 followed by ZOL at the day 2 (sequence A) or the reverse (sequence B). Patients were evaluated for adverse events and serum IL-8, MMP-2 and MMP-9 were evaluated prior and after therapy with the two sequences of administration of DTX and ZOL. CONCLUSIONS: The bi-weekly combination of DTX (50 mg/m(2)) followed by ZOL was feasible and show promising anti-tumor activity.