Metronomic administration of Zoledronic Acid and Taxotere combination in castration resistant prostate cancer patients: Phase I ZANTE trial

Abstract

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 ANd TaxoterE combination (ZANTE trial) in 2 different sequences was conducted in HRPC.

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 50mg/m2) in combination with a fixed dose of ZOL (2mg), 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.

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.

Conclusions. The bi-weekly combination of DTX (50mg/m2) followed by ZOL was feasible and show promising anti-tumor activity.