Annals of Oncology 10:311-316, 1999
© 1999 European Society for Medical Oncology
research-article |
Double-blind, randomised, placebo-controlled, dose-finding study of oral ibandronate in patients with metastatic bone disease
1Yorkshire Cancer Research Department of Clinical Oncology Weston Park Hospital, Sheffield, UK
2Boehringer Mannheim Therapeutics, Livingstone, Scotland and Mannheim Germany
3Department of Human Metabolism & Clinical Biochemistry Royal Hallamshire Hospital, Sheffield, UK
Dr R. E. Coleman, YCR Department of Clinical Oncology, Weston Park Hospital, Sheffield S10 2SJ, UK
Background: Bisphosphonates are an important component of the treatment of metastatic bone disease but more potent, oral formulations are required to improve the effectiveness and convenience of treatment. An oral formulation of the new bisphosphonate, ibandronate (BM 21.0955) has recently been developed.
Patients and methods: One hundred ten patients with bone metastases (77 breast, 16, prostate, 3 myeloma, 14 others) were recruited from a single institution to this double blind placebo-controlled evaluation of four oral dose levels (5, 10, 20 and 50 mg) of ibandronate. No changes in systemic anti-cancer treatment were allowed in the month before commencing treatment or during the study period. After an initial four-week tolerability phase, patients could continue on treatment for a futher three months without unblinding; patients initially allocated to placebo received ibandronate 50 mg. The primary endpoint was urinary calcium excretion (UCCR). Bone resorption was also assessed by measurement of pyridinoline (Pyr), deoxy-pyridinoline (Dpd), and the N-terminal (NTX) and C-terminal (Crosslaps) portions of the collagen crosslinking molecules.
Results: Two patients did not receive any trial medication thus, 108 patients were evaluable for safety. Ninety-two patients were evaluable for efficacy. A dose dependent reduction was observed in both UCCR and collagen crosslink excretion. At the 50 mg dose level, the percentage reductions from baseline in UCCR, Pyr, Dpd, Crosslaps and NTX were 71%, 28%, 39% 80% and 74% respectively.
One or more gastrointestinal (GI) adverse events occurring in the first month of treatment were reported by six (30%), seven (33%), nine (39%), nine (41%) and eleven (50%) patients at the placebo, 5,10, 20 and 50 mg dose levels respectively. One patient (20 mg dose) developed radiographically confirmed oesophageal ulceration. GI tolerability may have been adversely affected by concommitant administration of non-steroidal anti-inflammatory agents. Nine (8%) patients stopped treatment within the first month due to GI intolerability but these patients were evenly distributed across the five treatment groups. There was no difference in non-GI adverse events between groups.
Conclusions: Oral ibandronate has potent effects on the rate of bone resorption at doses which are generally well tolerated. Further development is appropriate to evaluate the effects of long-term administration in the prevention of metastatic bone disease and the management of established skeletal metastases.
bone resorption markers, ibandronate, metastatic bone disease
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Botteman, V. Barghout, J. Stephens, J. Hay, J. Brandman, and M. Aapro Cost effectiveness of bisphosphonates in the management of breast cancer patients with bone metastases Ann. Onc., July 1, 2006; 17(7): 1072 - 1082. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Conte and V. Guarneri In Response to Body Letter to the Editor Regarding "Safety of Intravenous and Oral Bisphosphonates and Compliance with Dosing Regimens" Oncologist, May 1, 2005; 10(5): 318 - 319. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Barrett, E. Worth, F. Bauss, and S. Epstein Ibandronate: A Clinical Pharmacological and Pharmacokinetic Update J. Clin. Pharmacol., September 1, 2004; 44(9): 951 - 965. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Conte and V. Guarneri Safety of Intravenous and Oral Bisphosphonates and Compliance With Dosing Regimens Oncologist, September 1, 2004; 9(suppl_4): 28 - 37. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Tripathy, M. Lichinitzer, A. Lazarev, S. A. MacLachlan, J. Apffelstaedt, M. Budde, and B. Bergstrom Oral ibandronate for the treatment of metastatic bone disease in breast cancer: efficacy and safety results from a randomized, double-blind, placebo-controlled trial Ann. Onc., May 1, 2004; 15(5): 743 - 750. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Ringe, A. Dorst, H. Faber, K. Ibach, and J. Preuss Three-monthly ibandronate bolus injection offers favourable tolerability and sustained efficacy advantage over two years in established corticosteroid-induced osteoporosis Rheumatology, June 1, 2003; 42(6): 743 - 749. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Berenson, R. A. Vescio, L. S. Rosen, J. M. VonTeichert, M. Woo, R. Swift, A. Savage, E. Givant, M. Hupkes, H. Harvey, et al. A Phase I Dose-ranging Trial of Monthly Infusions of Zoledronic Acid for the Treatment of Osteolytic Bone Metastases Clin. Cancer Res., March 1, 2001; 7(3): 478 - 485. [Abstract] [Full Text]
|
|
|
|
|
|
R. E. Coleman Management of Bone Metastases Oncologist, December 1, 2000; 5(6): 463 - 470. [Abstract] [Full Text]
|
|
|
|
 |
|
 K. Mannix, S. H. Ahmedzai, H. Anderson, M. Bennett, M. Lloyd-Williams, and A. Wilcock Using bisphosphonates to control the pain of bone metastases: evidence-based guidelines for palliative care Palliative Medicine, September 1, 2000; 14(6): 455 - 461. [Abstract] [PDF]
|
|