. 2009 Sep 21;3:27–40.

Table 3.

Efficacy of bisphosphonates in randomized, placebo-controlled trials of patients with bone metastases secondary to lung cancer or other solid tumors

Study	Study design	Drug	Primary endpoint	Efficacy results	Comments
Rosen et al 200347 Rosen et al 200448 (N = 773)	MC, R, DB, PC	ZOL 4 mg or 8 mg IV every 3 wk × 21 mo	Proportion with ≥1 SRE^a	9-mo analysis: ZOL 8/4 mg (p = 0.023), but not ZOL 4 mg (p = 0.127), reduced proportion with ≥1 SRE When HCM was included, both ZOL groups significantly reduced SRE ZOL 4 mg significantly extended time to first SRE (230 vs 163 d, p = 0.023) 21-mo analysis: ZOL 4 mg did not significantly reduce SRE when HCM was excluded When HCM was included, ZOL 4 mg significantly reduced SREs (39% vs 48%, p = 0.039) and increased median time to first SRE (236 vs 155 d, p = 0.009) ZOL 4 mg reduced risk of developing an SRE (including HCM) by 31%	Various solid tumors (approximately 50% NSCLC, 10% RCC, 10% SCLC) Protocol amendment reduced dose of ZOL from 8 mg to 4 mg due to renal toxicity Long-term (21 mo) follow-up confirms results demonstrated at 9 mo
Heras et al 200749 (N = 73)	R, PC	IBA 6 mg IV every 4 wk × 9 mo	Proportion with SRE^b	IBA significantly reduced proportion with SREs (39% vs 78%, p = 0.019) Delayed time to first SRE by 6 mo (p = 0.009)	Patients with metastatic bone disease from CRC
Piga et al 199850 (N = 50)	R, DB, PC	CLO 1600 mg PO daily × 1 yr	Symptom control, prevention of skeletal complications, and evolution of bone metastases	CLO did not significantly lower mean pain scores Patients receiving CLO had significantly lower analgesic requirement (p = 0.042)	Various poorly responsive solid tumors Short survival of most patients did not allow for adequate follow-up of bone lesions

Study

Study design

Drug

Primary endpoint

Efficacy results

Comments

Rosen et al 200347
Rosen et al 200448 (N = 773)

MC, R, DB, PC

ZOL 4 mg or 8 mg IV every 3 wk × 21 mo

Proportion with ≥1 SRE^a

9-mo analysis:

ZOL 8/4 mg (p = 0.023), but not ZOL 4 mg (p = 0.127), reduced proportion with ≥1 SRE
When HCM was included, both ZOL groups significantly reduced SRE
ZOL 4 mg significantly extended time to first SRE (230 vs 163 d, p = 0.023)

21-mo analysis:

ZOL 4 mg did not significantly reduce SRE when HCM was excluded
When HCM was included, ZOL 4 mg significantly reduced SREs (39% vs 48%, p = 0.039) and increased median time to first SRE (236 vs 155 d, p = 0.009)
ZOL 4 mg reduced risk of developing an SRE (including HCM) by 31%

Various solid tumors (approximately 50% NSCLC, 10% RCC, 10% SCLC)
Protocol amendment reduced dose of ZOL from 8 mg to 4 mg due to renal toxicity
Long-term (21 mo) follow-up confirms results demonstrated at 9 mo

Heras et al 200749 (N = 73)

R, PC

IBA 6 mg IV every 4 wk × 9 mo

Proportion with SRE^b

IBA significantly reduced proportion with SREs (39% vs 78%, p = 0.019)
Delayed time to first SRE by 6 mo (p = 0.009)

Patients with metastatic bone disease from CRC

Piga et al 199850 (N = 50)

R, DB, PC

CLO 1600 mg PO daily × 1 yr

Symptom control, prevention of skeletal complications, and evolution of bone metastases

CLO did not significantly lower mean pain scores
Patients receiving CLO had significantly lower analgesic requirement (p = 0.042)

Various poorly responsive solid tumors
Short survival of most patients did not allow for adequate follow-up of bone lesions

Defined as pathologic fracture, spinal cord compression, radiation therapy to bone, or surgery to bone, excluding HCM.

Defined as pathologic fracture, spinal cord compression, radiation therapy to bone, change in antineoplastic therapy, or surgery to bone.

Abbreviations: CLO, clodronate; CRC, colorectal cancer; DB, double-blind; HCM, hypercalcemia of malignancy; IBA, ibandronate; IV, intravenous; MC, multicenter; NSCLC, non–small cell lung cancer; PC, placebo-controlled; PO, oral; R, randomized; RCC, renal cell carcinoma; SCLC, small cell lung cancer; SRE, skeletal-related event; ZOL, zoledronic acid.