MEDICAL-TREATMENT OF TUMOR-INDUCED HYPERCALCEMIA AND TUMOR-INDUCED OSTEOLYSIS - CHALLENGES FOR FUTURE-RESEARCH

Tumor-induced hypercalcemia (TIH) and tumor-induced osteolysis (TIO) are essentially due to a marked increase in osteoclast-mediated bone resorption. Parathyroid-hormone-like protein plays an essential role in TIH, and maybe in TIO, but other substances, such as growth factors or cytokines, could contribute to the osteoclast activation and osteoblast inhibition secondary to the neoplastic infiltration of the skeleton. Treatment of TIH essentially consists of volume repletion and administration of potent anti-osteolytic drugs. Intravenous administration of the bisphosphonate clodronate or pamidronate is particularly useful for this. Pamidronate at a dose of 1.0-1.5 mg/kg as a single 4- to 24-h infusion can normalize serum calcium in about 90% of hypercalcemic cancer patients. The apparently low response rate of bone metastases to systemic antineoplastic therapy seems essentially to reflect the relative insensitivity of our current methods for assessing response in TIO. Quantitative evaluation of pain and of newly developed biochemical markers of bone turnover could be particularly useful for early assessment of response. Prolonged administration of oral pamidronate could reduce by almost one-half the complications of TIO, and iterative bisphosphonate infusions could induce a dramatic relief of bone pain in one-third and a sclerosis of lytic lesions in one-fourth of the cases. These data must, however, be confirmed in randomized blind trials and many questions remain unanswered.concerning the optimal therapeutic schemes. Despite these limitations, medical therapy of TIO by non-cytotoxic means has already become a reality.