Evaluation of a 24-hour infusion of etidronate disodium for the treatment of hypercalcemia of malignancy

J. F. Flores, R. K. Rude, R. A. Chapman, C. P. Belani, Alex Y Chang, J. D. Pritchard, J. V. Hoff

Research output: Contribution to journalArticle

Abstract

Background. Hypercalcemia is a serious and common complication of malignancy. Etidronate, a known inhibitor of osteoclastic bone resorption, is approved in the therapy of hypercalcemia of malignancy (HCM) at a dose of 7.5 mg/kg/day infused during a period of 2-4 hours on 3 consecutive days. A multicenter study was conducted to evaluate the safety and efficacy of a single 24-hour infusion of etidronate disodium in patients with HCM. Methods. Selected patients with HCM had disease refractory to at least 24-hours of intravenous fluid (more than 3 l/day) with two albumin-adjusted serum calcium concentrations greater than 11.5 mg/dl drawn 24 hours apart before etidronate treatment. Thirty patients were enrolled; 13 received 25 mg/kg for 24 hours, 12 received 30 mg/kg for 24-hours, 3 received incorrect doses (2 overdoses, and 1 underdose) and 2 died of disease-related complications before day 7. Of the 25 evaluable patients, 15 were men and 10 were women. Median age was 53 years (range, 20-75 years). Twelve patients (6 in each treatment group) had confirmed skeletal metastases. Results. During the week after treatment, the 25 mg/kg group had adjusted serum calcium levels fall from a mean preinfusion baseline of 13.3 ± 0.3 mg/dl (plus or minus the standard error of the mean) to a mean nadir of 10.9 ± 0.4 mg/dl (the average of each patient's lowest calcium values). The 30 mg/kg group had adjusted serum calcium levels fall from a mean preinfusion baseline of 13.8 ± 0.4 mg/dl to a mean nadir of 10.5 ± 0.3 mg/dl. The average day that nadir occurred was day 5.7 for the 25 mg/kg group and day 5.6 for the 30 mg/kg group. The mean maximum reduction (delta) derived from the patients' nadirs in the 25 mg/kg dose group was 2.5 ± 0.4 mg/dl and 3.3 ± 0.3 mg/dl for the 30 mg/kg dose. Time to effect (either a partial response defined as a 15% or greater decrease in the adjusted serum calcium from the preinfusion value or a complete eucalcemic response defined as a reduction to the laboratory's eucalcemic range) occurred on average on day 4.6 in the 25 mg/kg group and day 3.7 in the 30 mg/kg group. Nine of the 13 (69%) patients in the 25 mg/kg treatment group had either partial or complete response to the 24-hour infusion. Five of these patients (38% of the 13 patients) of the 25 mg/kg group had serum calcium levels fall to their laboratory's eucalcemic range before day 7 (a complete response), 4 (31%) had partial response only, and 4 had no response. In the 30 mg/kg group, 11 of 12 (92%) patients had at least partial responses. Eight of the 12 (67%) patients had adjusted serum calcium concentrations fall to the eucalcemic range by day 7, 3 (25%) had a partial response, and 1 had no response. Reported adverse experiences generally were attributable to the underlying disease. The reduction in the serum calcium throughout the week for the 30 mg/kg dose group was significantly greater than that for the 25 mg/kg group (analysis of variance, P <0.0001). Conclusions. Etidronate, when administered intravenously at 30 mg/kg during a period of 24 hours, apparently was safe and effective in this study for treatment of hypercalcemia in patients with a wide variety of tumor types. This regimen may offer a more convenient method of administration than does standard etidronate therapy for the treatment of HCM.

Original languageEnglish (US)
Pages (from-to)2527-2534
Number of pages8
JournalCancer
Volume73
Issue number10
DOIs
StatePublished - 1994
Externally publishedYes

Fingerprint

Etidronic Acid
Hypercalcemia
Neoplasms
Calcium
Therapeutics
Serum
Bone Density Conservation Agents
Serum Albumin
Multicenter Studies

Keywords

  • bisphosphonates
  • etidronate disodium
  • hypercalcemia
  • malignancy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Evaluation of a 24-hour infusion of etidronate disodium for the treatment of hypercalcemia of malignancy. / Flores, J. F.; Rude, R. K.; Chapman, R. A.; Belani, C. P.; Chang, Alex Y; Pritchard, J. D.; Hoff, J. V.

In: Cancer, Vol. 73, No. 10, 1994, p. 2527-2534.

Research output: Contribution to journalArticle

Flores, J. F. ; Rude, R. K. ; Chapman, R. A. ; Belani, C. P. ; Chang, Alex Y ; Pritchard, J. D. ; Hoff, J. V. / Evaluation of a 24-hour infusion of etidronate disodium for the treatment of hypercalcemia of malignancy. In: Cancer. 1994 ; Vol. 73, No. 10. pp. 2527-2534.
@article{1a661a6d238d46c5a3895e7d55e9347d,
title = "Evaluation of a 24-hour infusion of etidronate disodium for the treatment of hypercalcemia of malignancy",
abstract = "Background. Hypercalcemia is a serious and common complication of malignancy. Etidronate, a known inhibitor of osteoclastic bone resorption, is approved in the therapy of hypercalcemia of malignancy (HCM) at a dose of 7.5 mg/kg/day infused during a period of 2-4 hours on 3 consecutive days. A multicenter study was conducted to evaluate the safety and efficacy of a single 24-hour infusion of etidronate disodium in patients with HCM. Methods. Selected patients with HCM had disease refractory to at least 24-hours of intravenous fluid (more than 3 l/day) with two albumin-adjusted serum calcium concentrations greater than 11.5 mg/dl drawn 24 hours apart before etidronate treatment. Thirty patients were enrolled; 13 received 25 mg/kg for 24 hours, 12 received 30 mg/kg for 24-hours, 3 received incorrect doses (2 overdoses, and 1 underdose) and 2 died of disease-related complications before day 7. Of the 25 evaluable patients, 15 were men and 10 were women. Median age was 53 years (range, 20-75 years). Twelve patients (6 in each treatment group) had confirmed skeletal metastases. Results. During the week after treatment, the 25 mg/kg group had adjusted serum calcium levels fall from a mean preinfusion baseline of 13.3 ± 0.3 mg/dl (plus or minus the standard error of the mean) to a mean nadir of 10.9 ± 0.4 mg/dl (the average of each patient's lowest calcium values). The 30 mg/kg group had adjusted serum calcium levels fall from a mean preinfusion baseline of 13.8 ± 0.4 mg/dl to a mean nadir of 10.5 ± 0.3 mg/dl. The average day that nadir occurred was day 5.7 for the 25 mg/kg group and day 5.6 for the 30 mg/kg group. The mean maximum reduction (delta) derived from the patients' nadirs in the 25 mg/kg dose group was 2.5 ± 0.4 mg/dl and 3.3 ± 0.3 mg/dl for the 30 mg/kg dose. Time to effect (either a partial response defined as a 15{\%} or greater decrease in the adjusted serum calcium from the preinfusion value or a complete eucalcemic response defined as a reduction to the laboratory's eucalcemic range) occurred on average on day 4.6 in the 25 mg/kg group and day 3.7 in the 30 mg/kg group. Nine of the 13 (69{\%}) patients in the 25 mg/kg treatment group had either partial or complete response to the 24-hour infusion. Five of these patients (38{\%} of the 13 patients) of the 25 mg/kg group had serum calcium levels fall to their laboratory's eucalcemic range before day 7 (a complete response), 4 (31{\%}) had partial response only, and 4 had no response. In the 30 mg/kg group, 11 of 12 (92{\%}) patients had at least partial responses. Eight of the 12 (67{\%}) patients had adjusted serum calcium concentrations fall to the eucalcemic range by day 7, 3 (25{\%}) had a partial response, and 1 had no response. Reported adverse experiences generally were attributable to the underlying disease. The reduction in the serum calcium throughout the week for the 30 mg/kg dose group was significantly greater than that for the 25 mg/kg group (analysis of variance, P <0.0001). Conclusions. Etidronate, when administered intravenously at 30 mg/kg during a period of 24 hours, apparently was safe and effective in this study for treatment of hypercalcemia in patients with a wide variety of tumor types. This regimen may offer a more convenient method of administration than does standard etidronate therapy for the treatment of HCM.",
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author = "Flores, {J. F.} and Rude, {R. K.} and Chapman, {R. A.} and Belani, {C. P.} and Chang, {Alex Y} and Pritchard, {J. D.} and Hoff, {J. V.}",
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TY - JOUR

T1 - Evaluation of a 24-hour infusion of etidronate disodium for the treatment of hypercalcemia of malignancy

AU - Flores, J. F.

AU - Rude, R. K.

AU - Chapman, R. A.

AU - Belani, C. P.

AU - Chang, Alex Y

AU - Pritchard, J. D.

AU - Hoff, J. V.

PY - 1994

Y1 - 1994

N2 - Background. Hypercalcemia is a serious and common complication of malignancy. Etidronate, a known inhibitor of osteoclastic bone resorption, is approved in the therapy of hypercalcemia of malignancy (HCM) at a dose of 7.5 mg/kg/day infused during a period of 2-4 hours on 3 consecutive days. A multicenter study was conducted to evaluate the safety and efficacy of a single 24-hour infusion of etidronate disodium in patients with HCM. Methods. Selected patients with HCM had disease refractory to at least 24-hours of intravenous fluid (more than 3 l/day) with two albumin-adjusted serum calcium concentrations greater than 11.5 mg/dl drawn 24 hours apart before etidronate treatment. Thirty patients were enrolled; 13 received 25 mg/kg for 24 hours, 12 received 30 mg/kg for 24-hours, 3 received incorrect doses (2 overdoses, and 1 underdose) and 2 died of disease-related complications before day 7. Of the 25 evaluable patients, 15 were men and 10 were women. Median age was 53 years (range, 20-75 years). Twelve patients (6 in each treatment group) had confirmed skeletal metastases. Results. During the week after treatment, the 25 mg/kg group had adjusted serum calcium levels fall from a mean preinfusion baseline of 13.3 ± 0.3 mg/dl (plus or minus the standard error of the mean) to a mean nadir of 10.9 ± 0.4 mg/dl (the average of each patient's lowest calcium values). The 30 mg/kg group had adjusted serum calcium levels fall from a mean preinfusion baseline of 13.8 ± 0.4 mg/dl to a mean nadir of 10.5 ± 0.3 mg/dl. The average day that nadir occurred was day 5.7 for the 25 mg/kg group and day 5.6 for the 30 mg/kg group. The mean maximum reduction (delta) derived from the patients' nadirs in the 25 mg/kg dose group was 2.5 ± 0.4 mg/dl and 3.3 ± 0.3 mg/dl for the 30 mg/kg dose. Time to effect (either a partial response defined as a 15% or greater decrease in the adjusted serum calcium from the preinfusion value or a complete eucalcemic response defined as a reduction to the laboratory's eucalcemic range) occurred on average on day 4.6 in the 25 mg/kg group and day 3.7 in the 30 mg/kg group. Nine of the 13 (69%) patients in the 25 mg/kg treatment group had either partial or complete response to the 24-hour infusion. Five of these patients (38% of the 13 patients) of the 25 mg/kg group had serum calcium levels fall to their laboratory's eucalcemic range before day 7 (a complete response), 4 (31%) had partial response only, and 4 had no response. In the 30 mg/kg group, 11 of 12 (92%) patients had at least partial responses. Eight of the 12 (67%) patients had adjusted serum calcium concentrations fall to the eucalcemic range by day 7, 3 (25%) had a partial response, and 1 had no response. Reported adverse experiences generally were attributable to the underlying disease. The reduction in the serum calcium throughout the week for the 30 mg/kg dose group was significantly greater than that for the 25 mg/kg group (analysis of variance, P <0.0001). Conclusions. Etidronate, when administered intravenously at 30 mg/kg during a period of 24 hours, apparently was safe and effective in this study for treatment of hypercalcemia in patients with a wide variety of tumor types. This regimen may offer a more convenient method of administration than does standard etidronate therapy for the treatment of HCM.

AB - Background. Hypercalcemia is a serious and common complication of malignancy. Etidronate, a known inhibitor of osteoclastic bone resorption, is approved in the therapy of hypercalcemia of malignancy (HCM) at a dose of 7.5 mg/kg/day infused during a period of 2-4 hours on 3 consecutive days. A multicenter study was conducted to evaluate the safety and efficacy of a single 24-hour infusion of etidronate disodium in patients with HCM. Methods. Selected patients with HCM had disease refractory to at least 24-hours of intravenous fluid (more than 3 l/day) with two albumin-adjusted serum calcium concentrations greater than 11.5 mg/dl drawn 24 hours apart before etidronate treatment. Thirty patients were enrolled; 13 received 25 mg/kg for 24 hours, 12 received 30 mg/kg for 24-hours, 3 received incorrect doses (2 overdoses, and 1 underdose) and 2 died of disease-related complications before day 7. Of the 25 evaluable patients, 15 were men and 10 were women. Median age was 53 years (range, 20-75 years). Twelve patients (6 in each treatment group) had confirmed skeletal metastases. Results. During the week after treatment, the 25 mg/kg group had adjusted serum calcium levels fall from a mean preinfusion baseline of 13.3 ± 0.3 mg/dl (plus or minus the standard error of the mean) to a mean nadir of 10.9 ± 0.4 mg/dl (the average of each patient's lowest calcium values). The 30 mg/kg group had adjusted serum calcium levels fall from a mean preinfusion baseline of 13.8 ± 0.4 mg/dl to a mean nadir of 10.5 ± 0.3 mg/dl. The average day that nadir occurred was day 5.7 for the 25 mg/kg group and day 5.6 for the 30 mg/kg group. The mean maximum reduction (delta) derived from the patients' nadirs in the 25 mg/kg dose group was 2.5 ± 0.4 mg/dl and 3.3 ± 0.3 mg/dl for the 30 mg/kg dose. Time to effect (either a partial response defined as a 15% or greater decrease in the adjusted serum calcium from the preinfusion value or a complete eucalcemic response defined as a reduction to the laboratory's eucalcemic range) occurred on average on day 4.6 in the 25 mg/kg group and day 3.7 in the 30 mg/kg group. Nine of the 13 (69%) patients in the 25 mg/kg treatment group had either partial or complete response to the 24-hour infusion. Five of these patients (38% of the 13 patients) of the 25 mg/kg group had serum calcium levels fall to their laboratory's eucalcemic range before day 7 (a complete response), 4 (31%) had partial response only, and 4 had no response. In the 30 mg/kg group, 11 of 12 (92%) patients had at least partial responses. Eight of the 12 (67%) patients had adjusted serum calcium concentrations fall to the eucalcemic range by day 7, 3 (25%) had a partial response, and 1 had no response. Reported adverse experiences generally were attributable to the underlying disease. The reduction in the serum calcium throughout the week for the 30 mg/kg dose group was significantly greater than that for the 25 mg/kg group (analysis of variance, P <0.0001). Conclusions. Etidronate, when administered intravenously at 30 mg/kg during a period of 24 hours, apparently was safe and effective in this study for treatment of hypercalcemia in patients with a wide variety of tumor types. This regimen may offer a more convenient method of administration than does standard etidronate therapy for the treatment of HCM.

KW - bisphosphonates

KW - etidronate disodium

KW - hypercalcemia

KW - malignancy

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