METHYLPENTYLAMINOPROPYLIDENEBISPHOSPHONATE (BM-21.0955) - A NEW POTENT AND SAFE BISPHOSPHONATE FOR THE TREATMENT OF CANCER-ASSOCIATED HYPERCALCEMIA

Bisphosphonates have been shown to be effective in lowering serum calc ium levels in patients with cancer-associated hypercalcemia. oxy-3-(me thylpentylamino)propylidenebisphosphonate (BM 21.0955) was developed a s a third generation bisphosphonate and has been recently proven effec tive in animals and in patients with Paget's disease or tumor osteolys is. Thirty-six patients with cancer-associated hypercalcemia were trea ted with increasing doses (0.2-2.0 mg) of BM 21.0955 by single i.v. in fusion over 4 h in a phase I trial. Six patients were rejected from an alysis due to concomitant treatment with other bisphosphonates or chem otherapy. After rehydration and infusion of BM 21.0955 the mean serum calcium levels fell significantly (P < 0.001), from 3.29 +/- 0.49 mmol /l to 3.04 +/- 0.44 mmol/l until day 2 and normalized on day 6 (2.66 /- 0.33 mmol/l). Serum calcium was reduced in all patients and normali zed in 16. No symptomatic hypocalcemia occurred. Mean serum creatinine decreased significantly (P < 0.01 from 1.25 +/- 0.58 mg/dl (day 0) to 1.05 +/- 0.37 mg/dl (day 6). The mean urinary calcium/creatinine conc entration fell significantly (P < 0.001), from 1.90 +/- 1.16 mM/mM (da y 0) to 0.37 +/- 0.34 mM/mM/I (day 6). There were no subjective drug-r elated side effects during or after the infusion. Thirteen patients ha d elevations of morning body temperature above 38-degrees-C. This was due to confirmed infections in five patients and possibly drug- or tum or-related in the other eight. We conclude from these preliminary resu lts that a single infusion of BM 21.0955 is an effective and safe way to treat cancer-associated hypercalcemia.