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

Gaetano Facchini, Michele Caraglia, Alessandro Morabito, Monica Marra, Maria C. Piccirillo, Anna M. Bochicchio, Stefano Striano, Luigi Marra, Guglielmo Nasti, Ettore Ferrari, Davide Leopardo, Giovanni Vitale, Davide Gentilini, Anna Tortoriello, Alfonso Catalano, Alfredo Budillon, Franco Perrone, Rosario V. Iaffaioli

Research output: Contribution to journalArticle

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. 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/m2) 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/m2) followed by ZOL was feasible and show promising antitumor activity.

Original languageEnglish
Pages (from-to)543-548
Number of pages6
JournalCancer Biology and Therapy
Volume10
Issue number6
DOIs
Publication statusPublished - Sep 15 2010

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Keywords

  • Bone metastases
  • Docetaxel
  • Interleukin-8
  • Matrix metalloproteinases
  • Prostate cancer
  • Zoledronic acid

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology

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