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 < or = 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). More 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 < or = 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 day 12, 7 patients with elevated PTHrP were still hypercalcemic. Although a comparable number of patients in the two groups received cytostatic treatment after 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, an extremely poor prognosis.
Pecherstorfer
M
M
Department of Oncology, Lainz Hospital, Vienna, Austria.
Schilling
T
T
Blind
E
E
Zimmer-Roth
I
I
Baumgartner
G
G
Ziegler
R
R
Raue
F
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000097:blood* / Q000188:drug therapy; D000077557:Ibandronic Acid; D008017:Life Expectancy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D000077268:Pamidronate; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000032:analysis*; D015996:Survival Rate
D000970:Antineoplastic Agents; D004164:Diphosphonates; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D000077268:Pamidronate; D000077557:Ibandronic Acid