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 calcium levels in patients with cancer-associated hypercalcemia. 1-Hydroxy-3-(methylpentylamino)propylidenebisphosphonate (BM 21.0955) was developed as a third generation bisphosphonate and has been recently proven effective in animals and in patients with Paget's disease or tumor osteolysis. Thirty-six patients with cancer-associated hypercalcemia were treated with increasing doses (0.2-2.0 mg) of BM 21.0955 by single i.v. infusion over 4 h in a phase I trial. Six patients were rejected from analysis due to concomitant treatment with other bisphosphonates or chemotherapy. 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 normalized 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 concentration fell significantly (P < 0.001), from 1.90 +/- 1.16 mM/mM (day 0) to 0.37 +/- 0.34 mM/mM/l (day 6). There were no subjective drug-related side effects during or after the infusion. Thirteen patients had elevations of morning body temperature above 38 degrees C. This was due to confirmed infections in five patients and possibly drug- or tumor-related in the other eight. We conclude from these preliminary results that a single infusion of BM 21.0955 is an effective and safe way to treat cancer-associated hypercalcemia.
Wüster
C
C
Department of Internal Medicine I, University of Heidelberg, Germany.
Schöter
K H
KH
Thiébaud
D
D
Manegold
C
C
Krahl
D
D
Clemens
M R
MR
Ghielmini
M
M
Jaeger
P
P
Scharla
S H
SH
D000368:Aged; D001862:Bone Resorption / Q000188:drug therapy; D002118:Calcium / Q000097:blood* / Q000652:urine; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy* / Q000209:etiology; D000077557:Ibandronic Acid; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*
D004164:Diphosphonates; D002118:Calcium; D000077557:Ibandronic Acid