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

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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)⩾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 µg/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. We conclude that DDP is an effective agent for the treatment of MAHH, through a mechanism distinct from its antitumor cytotoxic effect and its potential to produce hypomagnesemia.