title: Palliative pamidronate treatment in patients with bone metastases from breast cancer.
abstract: OBJECTIVE
  An open, randomized study was performed to assess the effects of supportive pamidronate treatment on morbidity from bone metastases in breast cancer patients.
  
  
  METHODS
  Eighty-one pamidronate patients and 80 control patients were monitored for a median of 18 and 21 months, respectively, for events of skeletal morbidity and the radiologic course of metastatic bone disease. The oral pamidronate dose was 600 mg/d (high dose [HD]) during the earliest study years, then changed to 300 mg/d (low dose [LD]) because of gastrointestinal toxicity. Twenty-nine of 81 pamidronate (HD/LD) patients first received 600 mg/d and were then changed to 300 mg/d; 52 of 81 pamidronate LD patients received 300 mg/d throughout the study. Tumor treatment was unrestricted.
  
  
  RESULTS
  An overall intent-to-treat analysis was performed. In the pamidronate group, the occurrence of hypercalcemia, severe bone pain, and symptomatic impending fractures decreased by 65%, 30%, and 50%, respectively; event-rates of systemic treatment and radiotherapy decreased by 35% (P < or = .02). The event-free period (EFP), radiologic course of disease, and survival did not improve. Subgroup analyses suggested a dose-dependent treatment effect. Compared with their controls, in pamidronate HD/LD patients, events occurred 60% to 90% less frequently (P < or = .03) and the EFP was prolonged (P = .002). In pamidronate LD patients, event-rates decreased by 15% to 45% (P < or = .04). Gastrointestinal toxicity of pamidronate caused a 23% drop-out rate, but other cancer-associated factors seemed to contribute to this toxicity.
  
  
  CONCLUSIONS
  Pamidronate treatment of breast cancer patients efficaciously reduced skeletal morbidity. The effect appeared to be dose-dependent. Further research on dose and mode of treatment is mandatory.
authors.affiliation: Department of Clinical Oncology, Leiden University Hospital, The Netherlands.
authors.forename: A T
authors.initials: AT
authors.lastname: van Holten-Verzantvoort
authors.forename: H M
authors.initials: HM
authors.lastname: Kroon
authors.forename: O L
authors.initials: OL
authors.lastname: Bijvoet
authors.forename: F J
authors.initials: FJ
authors.lastname: Cleton
authors.forename: L V
authors.initials: LV
authors.lastname: Beex
authors.forename: G
authors.initials: G
authors.lastname: Blijham
authors.forename: J
authors.initials: J
authors.lastname: Hermans
authors.forename: J P
authors.initials: JP
authors.lastname: Neijt
authors.forename: S E
authors.initials: SE
authors.lastname: Papapoulos
authors.forename: H P
authors.initials: HP
authors.lastname: Sleeboom
mesh_terms: D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000473:pathology*; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D010166:Palliative Care; D000077268:Pamidronate; D011788:Quality of Life; D012044:Regression Analysis; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D004164:Diphosphonates; D000077268:Pamidronate