TABLE I.

Summary of bisphosphonate trials in breast cancer: agents approved in Canada

Trial	Patients (n)	Primary endpoints	Results	p Value
Clodronate versus placebo
Paterson et al., 199320	173	Hypercalcemia, vertebral and non-vertebral fractures, requirement for radiotherapy for bone pain	218.6 vs. 304.8 events per 100 patient–years	<0.001
Tubiana–Hulin et al., 200121	144	New bone events (hypercalcemia > 3 mmol/L), new or increased bone pain, radiotherapy for control of bone pain, pathologic fractures (including spinal cord compression), or death because of bone metastases	Prolonged time to new bone events: 244 days vs. 180 days	0.05
Pamidronate versus placebo
Hortobagyi et al., 199822	382	Skeletal complications (pathologic fractures, spinal cord compression with vertebral compression fracture, need for surgery for pathologic fractures or spinal cord compression, need for radiation to bone)	Prolonged median time to first skeletal complication: 13.9 months vs. 7.0 months	<0.001
Theriault et al., 199923	372	Skeletal morbidity rate, survival rate	Decreased skeletal morbidity rate at cycles 12, 18, and 24	0.028
				0.023
				0.008
Lipton et al., 20009 (combined analysis and 24-month extension of two trials)	754	Overall skeletal morbidity rate	↓ 35% (2.4 events vs. 3.7 events per year)	<0.001
		Skeletal complications	↓ 20% (51% vs. 64%)	<0.001
		Time to first skeletal complication	12.7 months vs. 7.0 months	<0.001
Zoledronate versus pamidronate
Rosen et al., 200114	1130a	Proportion of patients with 1 or more on-study skeletal-related events after 13 months	No significant difference in breast cancer patients receiving chemotherapy or hormonal therapy	ns
Rosen et al., 200324 (long-term efficacy and safety)	412b	Proportion of patients with 1 or more on-study skeletal-related events	No significant difference	ns

^aPatients with multiple myeloma (n = 158) also entered this trial.

^bPatients with multiple myeloma (n = 194) also entered this extension phase.

ns = nonsignificant.