Annals of Oncology Advance Access originally published online on September 28, 2007
Annals of Oncology 2008 19(3):420-432; doi:10.1093/annonc/mdm442
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Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel
1 Institut Multidisciplinaire d'Oncologie, Clinique de Genolier, Genolier, Switzerland
2 Malmö University Hospital, Department of Urology, Malmö, Sweden
3 CHU Brugmann & Institut J. Bordet, Université Libre de Bruxelles, Brussels, Belgium
4 Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield, UK
5 MD Anderson International, Madrid, Spain
6 Hospital de Santa Maria, Faculdade de Medicina de Lisboa, Lisboa, Portugal
7 Department of Medical Oncology, Perugia Hospital, Perugia, Italy
8 AZ Sint-Augustinus Cancer Center, Wilrijk, Belgium
9 Department of Surgery, Medical University of Vienna, Vienna, Austria
10 University of Washington, Seattle Cancer Care Alliance, Seattle, WA, USA
11 Department of Gynaecology, Philipps University Marburg, Marburg, Germany
12 Department of Breast Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
13 Gynaecology and Obstetrics Clinic, University of Kiel, Kiel, Germany
14 Milton S. Hershey Medical Center, Hershey, USA
15 Department of Medical Oncology, Centre Hospitalier A. Boulloche, Montbéliard Cedex, France
16 Department of Oncology, University of Calgary, Calgary, Alta, Canada
17 Service of Bone Diseases, University Hospital, Geneva, Switzerland
18 Centre Hospitalier de l'Université de Montréal, Montréal, Canada
19 Senologie-Zentrum Ostschweiz, Kantonsspital St Gallen, St Gallen, Switzerland
* Correspondence to: Dr M. Aapro, IMO Clinique de Genolier, Route du Muids 1, 1272 Genolier, Switzerland. Tel: +41-22-366-91-34; Fax: +41-22-366-91-31; E-mail: maapro{at}genolier.net
Bisphosphonates (BP) prevent, reduce, and delay cancer-related skeletal complications in patients, and have substantially decreased the prevalence of such events since their introduction. Today, a broad range of BP with differences in potency, efficacy, dosing, and administration as well as approved indications is available. In addition, results of clinical trials investigating the efficacy of BP in cancer treatment-induced bone loss (CTIBL) have been recently published. The purpose of this paper is to review the current evidence on the use of BP in solid tumours and provide clinical recommendations. An interdisciplinary expert panel of clinical oncologists and of specialists in metabolic bone diseases assessed the widespread evidence and information on the efficacy of BP in the metastatic and nonmetastatic setting, as well as ongoing research on the adjuvant use of BP. Based on available evidence, the panel recommends amino-bisphosphonates for patients with metastatic bone disease from breast cancer and zoledronic acid for patients with other solid tumours as primary disease. Dosing of BP should follow approved indications with adjustments if necessary. While i.v. administration is most often preferable, oral administration (clodronate, IBA) may be considered for breast cancer patients who cannot or do not need to attend regular hospital care. Early-stage cancer patients at risk of developing CTIBL should be considered for preventative BP treatment. The strongest evidence in this setting is now available for ZOL. Overall, BP are well-tolerated, and most common adverse events are influenza-like syndrome, arthralgia, and when used orally, gastrointestinal symptoms. The dose of BP may need to be adapted to renal function and initial creatinine clearance calculation is mandatory according to the panel for use of any BP. Subsequent monitoring is recommended for ZOL and PAM, as described by the regulatory authority guidelines. Patients scheduled to receive BP (mainly every 3–4 weeks i.v.) should have a dental examination and be advised on appropriate measures for reducing the risk of jaw osteonecrosis. BP are well established as supportive therapy to reduce the frequency and severity of skeletal complications in patients with bone metastases from different cancers.
Key words: bisphosphonates, bone, cancer, CTIBL, metastases, SRE
Received for publication August 6, 2007. Accepted for publication August 9, 2007.
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