title: Acute effects of pamidronate administration on serum levels of interleukin-6 in advanced solid tumour patients with bone metastases and their possible implications in the immunotherapy of cancer with interleukin-2.
abstract: Bisphosphonates are potent inhibitors of bone resorption and are commonly used in the treatment of bone metastases. In addition, they seem to influence cytokine secretion. Since the efficacy of IL-2 cancer immunotherapy, in part, depends on endogenous cytokine secretion, bisphosphonates could be effective in modulating IL-2 activity. High pretreatment levels of IL-6 seem to correlate with resistance to IL-2. On this basis, a pilot study was performed to evaluate the in vivo effects of the bisphosphonate, pamidronate, on blood levels of IL-6. The study included 7 patients with bone metastases due to solid tumours. Pamidronate was injected intravenously at 60 mg over 3 h. Venous blood samples were drawn before, at 1-h intervals during pamidronate infusion, then after 1 and 3 days. Mean serum levels of IL-6 significantly decreased during pamidronate infusion, then after 1 and 3 days, IL-6 mean levels still remained lower than control level, but differences were not significant. This preliminary study shows that pamidronate infusion induces a rapid but transient decline in IL-6 blood concentrations, and suggests a possible use of bisphosphonates to modulate the efficacy of IL-2 cancer immunotherapy.
authors.affiliation: Division of Radiation Oncology, San Gerardo Hospital, Monza, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Lissoni
authors.forename: M
authors.initials: M
authors.lastname: Cazzaniga
authors.forename: S
authors.initials: S
authors.lastname: Barni
authors.forename: M S
authors.initials: MS
authors.lastname: Perego
authors.forename: F
authors.initials: F
authors.lastname: Brivio
authors.forename: L
authors.initials: L
authors.lastname: Fumagalli
authors.forename: G
authors.initials: G
authors.lastname: Tancini
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy / Q000556:secondary*; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D000077268:Pamidronate; D010865:Pilot Projects
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates; D007376:Interleukin-2; D015850:Interleukin-6; D000077268:Pamidronate