Efficacy of Ibandronate in Metastatic Bone Disease: Review of Clinical Data

Bell, Richard

doi:10.1634/theoncologist.10-90001-8

Cited by 20 publications

(18 citation statements)

References 36 publications

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“…Many reviews have reported that ibandronate is able to reduce bone pain, to improve significantly global QoL and physical functioning, with an acceptable toxicity profile 5,[19][20][21][22][23] . Oral ibandronate is cost-effective for the management of bone metastases from breast cancer, providing effective reduction of skeletal-related events and avoiding resource use and costs associated with bisphosphonate infusion [24][25][26] .…”

Section: Discussionmentioning

confidence: 99%

Oral Ibandronate in Metastatic Bone Breast Cancer: The Florence University Experience and a Review of the Literature

Meattini¹,

Bruni²,

Scotti³

et al. 2010

Journal of Chemotherapy

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Ibandronate is an amino-bisphosphonate approved in metastatic breast cancer to reduce skeletal complications and to alleviate bone pain. we report our experience about the safety of oral ibandronate and review the literature.We treated 44 patients and administered 524 cycles of oral ibandronate (a single cycle was defined as a 50 mg capsule once daily for 28 days) with a median of 12 cycles (range 6-24). At a median follow-up of 18.5 months (range 6-28) the mean pain score decreased from 1.59 (SD+/-0.97) at baseline to 0.41 (SD+/-0.72) after 48 weeks of treatment. The mean analgesic score was 1.89 (SD+/-1.37) at baseline and 1.46 (SD+/-1.62) after 48 weeks of treatment. Ibandronate was generally well-tolerated; we had no Grade 3-4 adverse events. No patients had deterioration of renal function. No patients developed bisphosphonate-associated osteonecrosis of the jaw. Our experience confirmed that ibandronate may be a useful and safe co-analgesic to conventional treatments for bone pain in selected metastatic breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

Oral Ibandronate in Metastatic Bone Breast Cancer: The Florence University Experience and a Review of the Literature

Meattini¹,

Bruni²,

Scotti³

et al. 2010

Journal of Chemotherapy

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“…The goals of treatment for bone metastases are also to prevent disease-related skeletal complications, palliate pain, and maintain quality of life. Zoledronate, 104 pamidronate, clodronate, and ibandronate 105,106 have demonstrated efficacy compared with placebo.…”

Section: Clinical Applications Of Bisphosphonatesmentioning

confidence: 99%

Bisphosphonates: Mode of Action and Pharmacology

2007

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The profound effects of the bisphosphonates on calcium metabolism were discovered over 30 years ago, and they are now well established as the major drugs used for the treatment of bone diseases associated with excessive resorption. Their principal uses are for Paget disease of bone, myeloma, bone metastases, and osteoporosis in adults, but there has been increasing and successful application in pediatric bone diseases, notably osteogenesis imperfecta. Bisphosphonates are structural analogues of inorganic pyrophosphate but are resistant to enzymatic and chemical breakdown. Bisphosphonates inhibit bone resorption by selective adsorption to mineral surfaces and subsequent internalization by bone-resorbing osteoclasts where they interfere with various biochemical processes. The simpler, non-nitrogen-containing bisphosphonates (eg, clodronate and etidronate) can be metabolically incorporated into nonhydrolysable analogues of adenosine triphosphate (ATP) that may inhibit ATP-dependent intracellular enzymes. In contrast, the more potent, nitrogen-containing bisphosphonates (eg, pamidronate, alendronate, risedronate, ibandronate, and zoledronate) inhibit a key enzyme, farnesyl pyrophosphate synthase, in the mevalonate pathway, thereby preventing the biosynthesis of isoprenoid compounds that are essential for the posttranslational modification of small guanosine triphosphate (GTP)-binding proteins (which are also GTPases) such as Rab, Rho, and Rac. The inhibition of protein prenylation and the disruption of the function of these key regulatory proteins explains the loss of osteoclast activity. The recently elucidated crystal structure of farnesyl diphosphate reveals how bisphosphonates bind to and inhibit at the active site via their critical nitrogen atoms. Although bisphosphonates are now established as an important class of drugs for the treatment of many bone diseases, there is new knowledge about how they work and the subtle but potentially important differences that exist between individual bisphosphonates. Understanding these may help to explain differences in potency, onset and duration of action, and clinical effectiveness.www.pediatrics.org/cgi

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“…Several factors may explain these differences (Table 1). Clinical evidence for differences is discussed elsewhere [35].…”

Section: Rationale For Renal Safety Differencesmentioning

confidence: 99%

“…This difference may indicate that ibandronate has a broader renal safety margin and is less likely to cause renal damage Table 1. Preclinical data on bisphosphonates suggest that renal safety profiles differ [15,35] Abbreviation: LOEL, lowest observed effect level.…”

Section: Rationale For Renal Safety Differencesmentioning

confidence: 99%

Preclinical Perspectives on Bisphosphonate Renal Safety

2005

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Renal insufficiency is not rare in cancer patients who may receive nephrotoxic medications as antineo-plastic agents or for comorbid conditions. Thus, the choice of a particular bisphosphonate for patients with metastatic bone disease should be based not only on efficacy but also on the risk for renal deterioration. Some i.v. bisphosphonates have been associated with occasional renal toxicity in the clinical setting. Preclinical studies have also shown that there may be considerable differences among bisphosphonate renal safety profiles. Comparative studies show variations in the risk for histopathologic damage and the ability to cause cumulative toxicity during intermittent dosing. Reasons for the differences among bisphosphonates are not fully understood; however, research shows that they may be influenced by pharmacokinetic properties such as renal tissue half-life or protein binding and intracellular potency. Further preclinical analyses are needed to confirm and evaluate differences among bisphosphonates.

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Efficacy of Ibandronate in Metastatic Bone Disease: Review of Clinical Data

Cited by 20 publications

References 36 publications

Oral Ibandronate in Metastatic Bone Breast Cancer: The Florence University Experience and a Review of the Literature

Oral Ibandronate in Metastatic Bone Breast Cancer: The Florence University Experience and a Review of the Literature

Bisphosphonates: Mode of Action and Pharmacology

Preclinical Perspectives on Bisphosphonate Renal Safety

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