title: Prolonged administration of bisphosphonates is well-tolerated and effective for skeletal-related events in Chinese breast cancer patients with bone metastasis.
abstract: OBJECTIVE
  To evaluate the long-term tolerability and activity of prolonged administration of bisphosphonates (BPs) in breast cancer (BrCa) patients with bone metastasis (BM).
  
  
  METHODS
  We retrospectively analyzed safety data and activity of BPs in BrCa patients with BM who had received intravenous BPs for >24 months. Renal toxicity, osteonecrosis of the jaw (ONJ), and hypocalcemia were assessed. In addition, levels of creatinine (Cr) and calcium (Ca) in pre- and post-treatment sera were examined. The following parameters were also analyzed: the proportion of patients with at least one skeletal-related event (SRE), the distribution of each type of SRE, and the skeletal morbidity rate (SMR).
  
  
  RESULTS
  181 patients from January 1, 2005 to May 31, 2009 were enrolled in the study. The median BP administration period was 36 (range: 25-133) months. Grades 1-2 and 3 renal toxicity occurred in 3.9% and 0.7% of patients, respectively. Only one patient was diagnosed with ONJ, the incidence rate of which was 0.6%. Hypocalcemia occurred in 29 patients (16.0%), most frequently after two years of BP therapy. Neither serum Cr levels nor the creatinine clearance rate were significantly increased by treatment. Furthermore, 50 patients (27.6%) experienced a new SRE between zero and 24 months after BP therapy. However, no notable increase in incidence rate of SREs was observed after the two years of BP treatment. Overall, 63 patients (34.8%) experienced at least one new SRE after initiation of BPs (p = 0.173). No significant difference was found among the different BP subgroups of pamidronate, ibandronate, and zoledronate. Radiation to bone was the most common cause of SREs (68.4%, 67/98). SMR was 0.10 events per year for 0-5 years after BP treatment.
  
  
  CONCLUSIONS
  This was the largest retrospective study of extended use of BPs in BrCa patients with BM. Intravenous administration of BPs was well-tolerated and remained active throughout the prolonged period of administration. The occurrence of SREs was similar among the pamidronate, ibandronate, and zoledronate subgroups after two years of BP treatment.
authors.affiliation: Department of Medical Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Ding
authors.forename: Ying
authors.initials: Y
authors.lastname: Fan
authors.forename: Fei
authors.initials: F
authors.lastname: Ma
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Jiayu
authors.initials: J
authors.lastname: Wang
authors.forename: Pin
authors.initials: P
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Yuan
authors.forename: Binghe
authors.initials: B
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000453:epidemiology; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000150:complications* / Q000532:radiotherapy / Q000556:secondary; D001943:Breast Neoplasms / Q000473:pathology*; D002681:China; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D006934:Hypercalcemia / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D006996:Hypocalcemia / Q000139:chemically induced / Q000453:epidemiology; D015994:Incidence; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced / Q000453:epidemiology; D008875:Middle Aged; D012189:Retrospective Studies; D013117:Spinal Cord Compression / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates