ACUTE EFFECTS OF PAMIDRONATE ADMINISTRATION ON SERUM LEVELS OF INTERLEUKIN-6 IN ADVANCED SOLID TUMOR PATIENTS WITH BONE METASTASES AND THEIR POSSIBLE IMPLICATIONS IN THE IMMUNOTHERAPY OF CANCER WITH INTERLEUKIN-2

Bisphosphonates are potent inhibitors of bone resorption and are commo nly used in the treatment of bone metastases. In addition, they seem t o influence cytokine secretion. Since the efficacy of IL-2 cancer immu notherapy, in part, depends on endogenous cytokine secretion, bisphosp honates could be effective in modulating IL-2 activity. High pretreatm ent 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 in cluded 7 patients with bone metastases due to solid tumours. Pamidrona te was injected intravenously at 60 mg over 3 h. Venous blood samples were drawn before, at I-h intervals during pamidronate infusion, then after 1 and 3 days. Mean serum levels of IL-6 significantly decreased during pamidronate infusion. After 1 and 3 days, IL-6 mean levels stil l remained lower than control level, but differences were not signific ant. 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 ca ncer immunotherapy. (C) 1997 Elsevier Science Ltd.