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.


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.
Facchini
Gaetano
G
Genito-Urinary Department, National Cancer Institute Fondazione G Pascale, Naples, Italy.
Caraglia
Michele
M
Morabito
Alessandro
A
Marra
Monica
M
Piccirillo
Maria C
MC
Bochicchio
Anna M
AM
Striano
Stefano
S
Marra
Luigi
L
Nasti
Guglielmo
G
Ferrari
Ettore
E
Leopardo
Davide
D
Vitale
Giovanni
G
Gentilini
Davide
D
Tortoriello
Anna
A
Catalano
Alfonso
A
Budillon
Alfredo
A
Perrone
Franco
F
Iaffaioli
Rosario V
RV
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
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