Oral ibandronate is as active as intravenous zoledronic acid for reducing bone turnover markers in women with breast cancer and bone metastases.
BACKGROUND
Phase III study comparing the effect of oral ibandronate and intravenous zoledronic acid on bone markers.


METHODS
Breast cancer patients with bone metastases received ibandronate 50 mg/day (n = 137) or zoledronic acid 4 mg every 4 weeks (n = 138) for 12 weeks. The primary end point was mean percentage change in serum levels of cross-linked C-terminal telopeptide of type I collagen (S-CTX) at week 12. Urinary CTX (U-CTX), bone alkaline phosphatase (ALP), amino-terminal procollagen propeptide of type I collagen (PINP) and osteocalcin (OC) were also measured and bone pain and safety assessed.


RESULTS
Both bisphosphonates significantly reduced S-CTX (mean ibandronate 76% +/- 29 (SD) versus mean zoledronic acid 73% +/- 47; P < 0.001 for both versus baseline) and U-CTX (ibandronate 78% +/- 50 versus zoledronic acid 86% +/- 17; P < 0.001). The difference in S-CTX between treatments was 0.6% (confidence interval -1.7% to 3.0%), which was within the prespecified noninferiority margin. Bone ALP, PINP and OC decreased by 26%-47% compared with baseline with both bisphosphonates. Compared with zoledronic acid, ibandronate patients reported fewer adverse events overall (65.0% versus 75.9%), and on days 1-3 (8.0% versus 47.5%), including less pyrexia (overall incidence 0% versus 16.8%) and bone pain (5.8% versus 12.4%).


CONCLUSIONS
Oral ibandronate was well tolerated and statistically noninferior to zoledronic acid for percentage change in the bone resorption marker, S-CTX.
Body
J-J
JJ
Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. jj.body@bordet.be
Lichinitser
M
M
Tjulandin
S
S
Garnero
P
P
Bergström
B
B
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000187:drug effects / Q000652:urine; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D024042:Collagen Type I / Q000032:analysis / Q000187:drug effects; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D000077557:Ibandronic Acid; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D008875:Middle Aged; D015675:Osteocalcin / Q000187:drug effects / Q000652:urine; D010446:Peptide Fragments / Q000187:drug effects / Q000652:urine; D010455:Peptides / Q000032:analysis / Q000187:drug effects; D011347:Procollagen / Q000187:drug effects / Q000652:urine; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; D007093:Imidazoles; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin; D000077211:Zoledronic Acid; D000469:Alkaline Phosphatase; D000077557:Ibandronic Acid