title: 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 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.
  
  
  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.
authors.affiliation: Genito-Urinary Department, National Cancer Institute Fondazione G Pascale, Naples, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Facchini
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
authors.forename: Alessandro
authors.initials: A
authors.lastname: Morabito
authors.forename: Monica
authors.initials: M
authors.lastname: Marra
authors.forename: Maria C
authors.initials: MC
authors.lastname: Piccirillo
authors.forename: Anna M
authors.initials: AM
authors.lastname: Bochicchio
authors.forename: Stefano
authors.initials: S
authors.lastname: Striano
authors.forename: Luigi
authors.initials: L
authors.lastname: Marra
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Nasti
authors.forename: Ettore
authors.initials: E
authors.lastname: Ferrari
authors.forename: Davide
authors.initials: D
authors.lastname: Leopardo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vitale
authors.forename: Davide
authors.initials: D
authors.lastname: Gentilini
authors.forename: Anna
authors.initials: A
authors.lastname: Tortoriello
authors.forename: Alfonso
authors.initials: A
authors.lastname: Catalano
authors.forename: Alfredo
authors.initials: A
authors.lastname: Budillon
authors.forename: Franco
authors.initials: F
authors.lastname: Perrone
authors.forename: Rosario V
authors.initials: RV
authors.lastname: Iaffaioli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects; D007262:Infusions, Intravenous; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D009919:Orchiectomy; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000601:surgery; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D016209:Interleukin-8; D043823:Taxoids; D000077143:Docetaxel; D000077211:Zoledronic Acid; D017430:Prostate-Specific Antigen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9