Affiliation:
1. Department of Oncology and Hematology, University Hospital, Modena, Italy
Abstract
Abstract
Learning Objectives
After completing this course, the reader will be able to:
Describe the differences between oral and i.v. bisphosphonate therapy in terms of safety and side effects. Explain the renal effects of long-term i.v. bisphosphonate treatment. Discuss the importance of patient compliance in long-term disease management.
Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com
Patients with advanced cancers—particularly breast and prostate cancers—are at high risk for bone metastasis, leading to accelerated bone resorption and clinically significant skeletal morbidity. Bisphosphonates are effective inhibitors of bone resorption and reduce the risk of skeletal complications in patients with bone metastases. The standard routes of administration for bisphosphonates used in clinical practice are either oral or i.v. infusion. Oral administration of bisphosphonates is complicated by poor bioavailability (generally <5%) and poor gastrointestinal tolerability. First-generation bisphosphonates, such as clodronate (Bonefos®; Anthra Pharmaceuticals; Princeton, NJ), must be administered at high oral doses (1,600–3,200 mg/day) to achieve therapeutic effects, which leads to poor tolerability and compliance with oral dosing regimens. Infusion of bisphosphonates is associated with dose- and infusion-rate-dependent effects on renal function. In particular, high bisphosphonate doses (e.g., 1,500 mg clodronate) can cause severe renal toxicity unless infused slowly over many hours. In contrast, the newer, more potent bisphosphonates effectively inhibit bone resorption at micromolar concentrations, and the small doses required can be administered via relatively short i.v. infusions without adversely affecting renal function. Zoledronic acid (Zometa®; Novartis Pharmaceuticals Corp.; East Hanover, NJ) is a new generation bisphosphonate, and the recommended dose of 4 mg can be safely infused over 15 minutes. The 90-mg dose of pamidronate (Aredia®; Novartis Pharmaceuticals Corp.) and the 6-mg dose of ibandronate (Bondronat®; Hoffmann-La Roche Inc.; Nutley, NJ) require 1- to 4-hour infusions. Intravenous bisphosphonates require less frequent dosing (once a month) and are generally well tolerated with long-term use in patients with bone metastases. Zoledronic acid has demonstrated the broadest clinical activity in patients with bone metastases.
Publisher
Oxford University Press (OUP)
Cited by
181 articles.
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