Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel

Abstract

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.

Current Management of Castrate-Resistant Prostate Cancer

“…Treatment is not recommended for men with a baseline creatinine clearance below 30 mL/min 39 . The optimal duration of zoledronic acid in men with castration-recurrent pca and bone metastases is undefined.…”

Prevalence of renal insufficiency in breast cancer patients and related pharmacological issues

“…In patients with evidence of renal deterioration during treatment, IV BP should be withheld and only resumed when serum creatinine returns to within 10% baseline 27 . In case of mild to moderate renal impairment (CrCl:30-60 ml/min) regulations recommend lower doses of zoledronate and longer infusion for pamidronate.…”

Definition and estimation of osteonecrosis of jaw (ONJ), and optimal duration of antiresorptive treatment in bone metastatic cancer patients: supplementary data from the denosumab extension study?

“…After reporting several cases of renal toxicity and ONJ, especially in patients exposed for longer time, since years 2006-2007 some guidelines indicated treatment with bisphosphonates for 1 or 2 years, and then Btailoring^the therapy, for both myeloma patients [22][23][24] and bone metastases of solid tumors [25]. Despite this, the ASCO did not change recommendations for bone metastatic breast cancers till 2011, after approval of denosumab [26]: it was underlined that BThere are no prospective clinical RCT data to support the continuation of bone-modifying agent therapy beyond 1 year^whereas in the summary table, at the voice BOptimal duration^it was reported BUnchanged in substance from 2003^(that is Bcontinued until evidence of substantial decline in a patient's general performance status.^) [26].…”