Cis-platinum treatment for malignancy-associated humoral hypercalcemia in an athymic mouse model

Abstract

We have established a model for malignancy-associated humoral hypercalcemia (MAHH) in athymic mice, utilizing a human squamous cell lung carcinoma. In the present studies, we evaluated cis-platinum (DDP), a cytotoxic agent known to produce hypomagnesemia, and occasionally hypocalcemia, in the treatment of MAHH. Upon development of significant hypercalcemia, defined as serum calcium (Ca) greater than or equal to 11.5 mg/dl, tumor-bearing mice received either normal saline (NS) alone (1.5 ml/day, i.p.), or NS + DDP. The DDP was given as a single dose of 6 micrograms/g body weight i.p. Serum Ca was determined on day 6 in surviving mice (6 of 10 survived in the NS-alone group; 7 of 10 survived in the NS + DDP group). Serum Ca (mean +/- SE) decreased from 14.3 +/- 0.46 to a nadir of 12.7 +/- 0.33 mg/dl in the NS-alone group, and from 13.5 +/- 0.46 to a nadir of 10.4 +/- 0.48 mg/dl in the NS + DDP group. Nadir serum Ca levels were significantly lower in the NS + DDP group (P = 0.003). Three of 7 surviving NS + DDP mice achieved normocalcemia, whereas none of the NS-alone animals became normocalcemic. Tumor volumes increased in all animals. There was no change in the serum Ca in 5 tumor-free mice treated with NS + DDP. There were no significant differences in serum magnesium levels among groups of control mice, tumor-free mice treated with NS + DDP, tumor-bearing mice treated with NS + DDP, and tumor-bearing mice treated with NS-alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypercalcemia of Malignancy

“…In this animal model, cisplatin administration decreased se¬ rum calcium levels without affecting serum magnesium levels or tumor vol¬ umes. 3 We have recently demonstrated that cisplatin has a direct inhibitory effect on bone résorption in vitro and believe this to be the most likely mech¬ anism for the observed hypocalcémie effects.4 Serum parathyroid hormone levels were not significantly affected by cisplatin therapy in the present study. Recent studies have, however, demonstrated that parathyroid hor-mone is rarely the factor responsible for the hypercalcemia of malignancy.5…”

To the Editor.—-Reply

“…3 We have recently demonstrated that cisplatin has a direct inhibitory effect on bone résorption in vitro and believe this to be the most likely mech¬ anism for the observed hypocalcémie effects.4 Serum parathyroid hormone levels were not significantly affected by cisplatin therapy in the present study. On the other hand, there was no change in serum magnesium level in patient 8, yet serum calcium decreased to a level of 2.02 mmol/L (8.1 mg/dL) with cisplatin therapy.…”

Treatment of Cancer-Associated Hypercalcemia With Cisplatin

“…Patients who had (1) serum calcium levels of greater than 11.5 mg/dL (2.87 mmol/L), (2) a diagnosis of malignant neo¬ plasm other than lymphoma or myeloma, and (3) correction of dehydration shown by serum urea nitrogen level under 20 mg/dL (7.1 mmol/L) and serum creatinine level under 2 mg/dL (180 µ /L) were evaluated for entry into the study. All potential study patients received 1 L of 0.9% sodium chloride every eight hours for at least a 24-hour period.…”