. 2009 Sep 21;3:27–40.

Table 2.

Efficacy of bisphosphonates in randomized, placebo-controlled trials of prostate cancer patients with bone metastases

Study	Study design	Drug	Primary endpoint	Efficacy results	Comments
Saad et al 200243 Saad et al 200444 (N = 643)	MC, R, DB, PC	ZOL 4 mg or 8 mg IV every 3 wk × 24 mo	Proportion with ≥1 SRE^a	15-mo analysis: Urinary markers of bone resorption significantly decreased in patients receiving ZOL (p = 0.001) ZOL significantly reduced SRE (44.2% vs 33.2%, p = 0.021) and SMR^b (p = 0.006), and increased median time to first SRE (p = 0.011) 24-mo analysis: ZOL significantly reduced SREs (38% vs 49%, p = 0.028) and increased median time to first SRE (p = 0.009) ZOL 4 mg produced 36% reduction in ongoing risk of SREs (p = 0.002)	Protocol amendment reduced dose of ZOL from 8 mg to 4 mg due to renal toxicity Only 122 patients completed total 24 mo of study
Small et al 200345 (N = 378)	MC, R, DB, PC	PAM 90 mg IV every 3 wk × 27 wk	Reduction in bone pain or analgesic use	No significant change from baseline pain scores 36% patients able to decrease or stabilize analgesic use	Pooled results of 2 double-blind randomized trials
Dearnaley et al 200346 (N = 311)	MC, R, DB, PC	CLO 2080 mg PO daily × maximum 3 yr	Symptomatic BPFS^c	Patients receiving CLO had longer symptomatic BPFS times (HR 0.79, 95% CI, 0.61–1.02, p = 0.066)	Patients were starting or responding to hormonal therapy PSA levels were lower among patients receiving CLO (p = 0.053)

Study

Study design

Drug

Primary endpoint

Efficacy results

Comments

Saad et al 200243
Saad et al 200444 (N = 643)

MC, R, DB, PC

ZOL 4 mg or 8 mg IV every 3 wk × 24 mo

Proportion with ≥1 SRE^a

15-mo analysis:

Urinary markers of bone resorption significantly decreased in patients receiving ZOL (p = 0.001)
ZOL significantly reduced SRE (44.2% vs 33.2%, p = 0.021) and SMR^b (p = 0.006), and increased median time to first SRE (p = 0.011)

24-mo analysis:

ZOL significantly reduced SREs (38% vs 49%, p = 0.028) and increased median time to first SRE (p = 0.009)
ZOL 4 mg produced 36% reduction in ongoing risk of SREs (p = 0.002)

Protocol amendment reduced dose of ZOL from 8 mg to 4 mg due to renal toxicity
Only 122 patients completed total 24 mo of study

Small et al 200345 (N = 378)

MC, R, DB, PC

PAM 90 mg IV every 3 wk × 27 wk

Reduction in bone pain or analgesic use

No significant change from baseline pain scores
36% patients able to decrease or stabilize analgesic use

Pooled results of 2 double-blind randomized trials

Dearnaley et al 200346 (N = 311)

MC, R, DB, PC

CLO 2080 mg PO daily × maximum 3 yr

Symptomatic BPFS^c

Patients receiving CLO had longer symptomatic BPFS times (HR 0.79, 95% CI, 0.61–1.02, p = 0.066)

Patients were starting or responding to hormonal therapy
PSA levels were lower among patients receiving CLO (p = 0.053)

Defined as pathologic bone fractures (vertebral or nonvertebral), spinal cord compression, surgery to bone, radiation therapy to bone (including the use of radioisotopes), or a change of antineoplastic therapy to treat bone pain.

Number of SREs^a divided by the time at risk in years.

Defined as the time from randomization to the development of symptomatic bone metastases (ie, the need to initiate further treatment) or to death from prostate cancer.

Abbreviations: BPFS, bone progression-free survival; CI, confidence interval; CLO, clodronate; DB, double blind; HR, hazard ratio; IV, intravenous; MC, multicenter; PAM, pamidronate; PC, placebo-controlled; PO, oral; PSA, prostate specific antigen; R, randomized; SMR, skeletal morbidity rate; SRE, skeletal-related event; ZOL, zoledronic acid.