The Oncologist 2006;11:841–848 www.TheOncologist.com S ymptom Management and S upportive Care Efficacy and Safety of Zoledronic Acid in Patients with Breast Cancer Metastatic to Bone: A Multicenter Clinical Trial Giacomo Cartenì, a Roberto Bordonaro, b Francesco Giotta, c Vito Lorusso, c Simona Scalone, d Vincenza Vinaccia, e Roberta Rondena, e Dino Amadori f a A.O.R.N.A. Cardarelli, Napoli, Italy; b Ospedale Vittorio Emanuele II, Catania, Italy; c Istituto Oncologico, Bari, Italy; d Centro di Riferimento Oncologico, Aviano, Italy; e Novartis Farma S.p.A, Origgio, Italy; f Ospedale Morgagni-Pierantoni, Forlì, Italy Key Words. Zoledronic acid • Bisphosphonates • Breast cancer • Bone metastases Correspondence: Dino Amadori, M.D., Ospedale Morgagni-Pierantoni, Divisione di Oncologia Medica, Via Forlanini 34, Forlì, 47100 Italy. Telephone: +39-0543-731737; Fax: +39-0543-731736; e-mail: segronco@ausl.fo.it Received March 9, 2006; accepted for publica- tion May 18, 2006. ©AlphaMed Press 1083-7159/2006/$20.00/0 Abstract Purpose. This study evaluated the efficacy and safety of zoledronic acid in breast cancer patients with newly diagnosed bone metastases. Materials and Methods. Patients diagnosed with bone metastases ≤ 6 weeks prior to first visit were enrolled. Zoledronic acid (4 mg) was administered via a 15-minute infusion every 3 or 4 weeks for 12 infusions. Skeletal-related events (SREs) were defined as patho- logic bone fractures, spinal cord compression, surgery to bone, radiation therapy to bone, and hypercalcemia of malignancy. Primary efficacy end points were the proportion of patients with at least one SRE and the time to first SRE. Secondary end points included pain, anal- gesic use, and quality of life. Results. Among 312 patients enrolled, 30% experi- enced at least one SRE during the 12-month study, and 22% experienced only one SRE. The median time to first SRE was not reached in the intent-to-treat population. Mean pain and analgesic scores declined from baseline, and quality-of-life scores remained stable to study end. The most frequently reported adverse events, regardless of relationship to study drug, were pyrexia (22%) and bone pain (10%). Serum creatinine levels did not sig- nificantly increase from baseline throughout the study. Conclusions. Breast cancer patients with newly diagnosed bone metastases who were treated with zole- dronic acid had a low incidence of SREs compared with patients who received placebo in randomized phase III trials, and pain was decreased from baseline. This study demonstrated the favorable risk:benefit ratio of zole- dronic acid for the prevention of skeletal complications. The Oncologist 2006;11:841–848 Introduction Each year nearly 800,000 women worldwide are diagnosed with breast cancer, and 314,000 die from the disease [1]. Globally, breast cancer is the most common type of cancer and the leading cause of cancer-related mortality in women [1]. Approximately 70% of patients with advanced breast cancer develop bone metastases [2]. Bone metastases are a common cause of skeletal complications, including severe bone pain requiring palliative radiotherapy, pathologic fractures, spinal cord compression, and hypercalcemia of malignancy (HCM). Because the median survival time for patients with breast cancer is 18–26 months after diagnosis of bone metastases, these patients are at risk for long-term skel- etal morbidity [3]. In fact, several studies have shown that, without effective bisphosphonate therapy, approximately 55% of patients are likely to experience at least one skeletal- related event (SRE) within 12 months of study entry [4–6]. Downloaded from https://academic.oup.com/oncolo/article/11/7/841/6397099 by guest on 20 June 2022