PARATHYROID HORMONE-RELATED PROTEIN AND LIFE EXPECTANCY IN HYPERCALCEMIC CANCER-PATIENTS

We determined the effect of raised serum levels of midregional (53-84) parathyroid hormone-related protein (PTHrP) on life expectancy in 59 cancer patients with first presentation of hypercalcemia. The patients were stratified according to the serum PtHrP levels measured on day 0 after fluid repletion prior to bisphosphonate therapy. Twenty-nine patients were assigned to group N (PTHrP less than or equal to 21 pmol/L) and 30 to group E (PTHrP > 21 pmol/L). Breast cancers were more common in group N, squamous cell cancers predominated in group E (p < 0.02). Mote patients with normal PTHrP had skeletal metastases, whereas group E was characterized by a higher incidence of prognostically unfavorable visceral involvement (p < 0.001). Bisphosphonates (pamidronate or BM.210955) were administered on day 0. Within one week, normocalcemia (serum calcium less than or equal to 2.6 mmol/L) was restored in 96% of patients in group N, compared to 70% of patients in group E (p < 0.01). On dry 12, 7 patients with elevated PTHrP were still hypercalcemic. Although a comparable number of patients in the two groups received cytostatic treatment alter day 12, objective tumor responses were seen only in group N (n=6; p < 0.05). Calculated from the first occurrence of hypercalcemia, the median survival was 66 days in group N and 33 days in group E (log-rank test: p=0.0456; Wilcoxon-Breslow test: p=0.0475). We conclude that in hypercalcemia of malignancy raised serum levels of PTHrP indicate a reduced hypocalcemic response to bisphosphonates, a more advanced tumor state and, therefore, on extremely poor prognosis.