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

• DOI: 10.4161/cbt.10.6.12611
• Publication Date: 2010-11-04T20:54:16Z
• Authors: Gaetano Facchini; Michele Caraglia; Alessandro Morabito; Monica Marra; Maria C. Piccirillo; Anna M. Bochicchio; Stefano Striano; Luigi Marra; Guglielmo Nasti; Ettore Ferrara; Giovanni Vitale; Davide Gentilini; Anna Tortoriello; Alfonso Catalano; Alfredo Budillon; Franco Perrone; Rosario V. Iaffaioli
• Keywords: Adult; Male; Infusions; Cancer Research; Neutropenia; Fever; Intravenou; 610; Docetaxel; Drug Administration Schedule; Dose-Response Relationship; 03 medical and health sciences; 0302 clinical medicine; Taxoid; Antineoplastic Combined Chemotherapy Protocols; 80 and over; Humans; Infusions, Intravenous; Imidazole; Zoledronic acid; Aged; Pharmacology; Aged, 80 and over; Prostate cancer; Antineoplastic Combined Chemotherapy Protocol; Diphosphonates; Dose-Response Relationship, Drug; Interleukin-8; Imidazoles; Anemia; Prostate-Specific Antigen; Middle Aged; 3. Good health; Matrix metalloproteinase; Feasibility Studie; Bone metastase; Treatment Outcome; Diphosphonate; Oncology; Matrix Metalloproteinase 9; Prostatic Neoplasm; Molecular Medicine; Feasibility Studies; Matrix Metalloproteinase 2; Drug; Orchiectomy; Human

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.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.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.The bi-weekly combination of DTX (50 mg/m(2)) followed by ZOL was feasible and show promising anti-tumor activity.