Plasma PTH and PTH-rP levels and clodronate therapy in cancer patients with hypercalcemia

To investigate the roles of parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTH-rP) in hypercalcemic patients with various malignancies, we measured the plasma levels of intact PTH and intact PTH-rP in five hypercalcemic patients with hematologic malignancies and 29 hypercalcemic patients with solid cancers. Ten eucalcemic cancer patients with either hepatocellular carcinoma or squamous cancer of the lung served as controls. The results showed a suppressed PTH level in all of the 34 hypercalcemic cancer patients. The PTH-rP levels were within normal limits (< 2.5 pg/mL) for all of the eucalcemic cancer controls, all of the five hematologic cancer patients with hypercalcemia, and only two out of the 29 hypercalcemic patients with solid cancers. The PTH-rP level was elevated in nearly all (27/29) hypercalcemic patients with or without bony metastasis. There was a good correlation between the corrected total serum calcium level and the natural log of PTH-rP level in 39 patients (10 eucalcemic and 29 hypercalcemic) with solid cancers (r = 0.75, p < 0.001). These results suggest that PTH-rP plays an important role in the hypercalcemia of patients with solid cancers, but this was not the case in our patients with hematologic malignancies. True ectopic secretion of PTH is unlikely in most of these patients. The mean serum total calcium levels of 17 hypercalcemic patients (13 solid cancers, four hematologic malignancies) dropped significantly after the third day of treatment with a new-generation bisphosphonate-clodronate product. This treatment consisted of 300 mg daily intravenous infusion for seven days, followed by oral administration (800 mg, bid) for the following three weeks.(ABSTRACT TRUNCATED AT 250 WORDS)