title: Dose-response study of alendronate sodium for the treatment of cancer-associated hypercalcemia.
abstract: OBJECTIVE
  A randomized, double-blind, dose-ranging study of single-dose intravenous (IV) therapy with alendronate sodium (aminohydroxybutylidene bisphosphonate) was performed in patients with cancer-associated hypercalcemia.
  
  
  METHODS
  Patients with hypercalcemia who had not received antitumor therapy in the preceding 7 days were treated with 48 hours of IV hydration. Patients with persistent hypercalcemia (albumin-corrected serum calcium concentration [CSCC] > or = 11.5 mg/dL) were randomly assigned to receive 2.5, 5, 10, or 15 mg of alendronate infused over 2 hours, or 10 mg of alendronate infused over 24 hours. Fifty-nine patients were treated and 50 patients were assessable for the dose-response relationship.
  
  
  RESULTS
  Normalization of CSCC (< or = 10.5 mg/dL) was achieved in 22%, 82%, 75%, and 90% of assessable patients in the 2.5-, 5-, 10- (2- and 24-hour groups pooled), and 15-mg dose groups, respectively, within 8 days of therapy. Doses > or = 5 mg were significantly superior to the 2.5-mg dose level (P < .05). There was no significant difference in the minimum CSCC achieved between the 2- and 24-hour infusions of the 10-mg dose. Based on an intent-to-treat analysis of all randomized patients, the overall complete response rate was 74% for dose levels greater than 2.5 mg. For assessable patients who responded to > or = 5 mg of alendronate, the estimated median duration of normocalcemia was 10 days (range, 1 to 25). The estimated median time to relapse (CSCC > 11.5 mg/dL) was 15 days from initial treatment and 12 days from initial response, respectively. Adverse events included a transient febrile response in 34% of patients and eight episodes of reversible elevations in serum transaminase levels among treated patients.
  
  
  CONCLUSIONS
  While a statistically significant dose-response relationship was not clearly evident at doses greater than 5 mg, single doses of > or = 5 mg alendronate sodium effectively lowered serum calcium concentrations and were well tolerated in the treatment of cancer-associated hypercalcemia.
authors.affiliation: Harvard Medical School, Boston, MA.
authors.forename: S R
authors.initials: SR
authors.lastname: Nussbaum
authors.forename: R P
authors.initials: RP
authors.lastname: Warrell
authors.forename: R
authors.initials: R
authors.lastname: Rude
authors.forename: J
authors.initials: J
authors.lastname: Glusman
authors.forename: J P
authors.initials: JP
authors.lastname: Bilezikian
authors.forename: A F
authors.initials: AF
authors.lastname: Stewart
authors.forename: M
authors.initials: M
authors.lastname: Stepanavage
authors.forename: J F
authors.initials: JF
authors.lastname: Sacco
authors.forename: S D
authors.initials: SD
authors.lastname: Averbuch
authors.forename: B J
authors.initials: BJ
authors.lastname: Gertz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate; D000704:Analysis of Variance; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy* / Q000209:etiology; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D016896:Treatment Outcome
chemical_list: D004164:Diphosphonates; D019386:Alendronate