Treatment Of Malignant Hypercalcemia Research Articles

Delayed hypocalcaemia following treatment of malignant hypercalcaemia with denosumab

Delayed hypocalcaemia following treatment of malignant hypercalcaemia with denosumab

A multicenter phase II trial of domestic product of zoledronic acid in the treatment of malignant hypercalcemia

Objective To evaluate the effect and safety of clinical use of zoledronic acid in the treatment of malignant hypercalcemia.

Bone mineral density in women with non-metastatic breast cancer: Effect of intravenous bisphosphonates given before adjuvant therapies

11038 Background: Adjuvant therapies shown survival improve of non-metastatic breast cancer (NMBC) patients, but they also decrease bone mineral density (BMD). Bisphosphonates are effective agents for the management of osteoporosis. Intravenous zoledronate, which is approved for the treatment of malignant hypercalcemia, multiple myeloma, and skeletal metastases, can suppress bone resorption and are often considered first-line therapy for the treatment of osteoporosis. We have analyzed the effects of chemotherapy on BMD of women with NMBC who received before adjuvant therapies intravenous bisphosphonates (zoledronic acid). Methods: We prospectively studied the effects of a single intravenous zoledronic acid dose (4 mg), on BMD of 74 women with NMBC (stage I-III), administred previous to the adjuvant therapies. The patients were referred to the Medical Oncology Service of University Hospital of Canary Islands between 2003 y 2006. Lumbar and hip BMD (g/cm2) was measured at diagnosis and after chemotherapy. The results were compared with a group of 80 patients with NMBC who received adjuvant therapy without intravenous bisphosphonates. Results: Breast cancer patients the median age was 52 ± 10 years old and the body mass index was 28,2 ± 5.5 kg/m2. At baseline there were not differences in BMD between the group that received bisphosphonates and the group with only chemotherapy at any of lumbar or femoral bone sites. In our study, the BMD after chemotherapy and intravenous bisphosphonates (n=74) significantly increased at femoral neck (0.805 ± 0.01, 0,826± 0.12; p=0.002) and trochanter (0.709 ± 0.01, 0.724 ± 0.01; p=0.002) and remained stable at lumbar, intertrochanter, total hip and Ward’s triangle; whether the group without bisphosphonates significantly decreased at lumbar (1.014 ± 0; 0.995 ± 0, p=0.0001), trochanter (0.701± 0; 0.690 ± 0, p=0,046), intertrochanter (1,095 ± 0; 1.078 ± 0, p=0.0001) and total hip (0,924 ± 0; 0.915 ± 0, p=0.046) areas (table). Conclusions: Women with NMBC are affected by early bone loss after adjuvant chemotherapy. Bisphosphonates intravenous (zoledronic acid) given before adjuvant therapy might be an effective treatment for this bone loss, increasing BMD or remaining stable. No significant financial relationships to disclose.

Three-Year Oral Clodronate Treatment Does Not Impair Mineralization of Newly Formed Bone—A Histomorphometric Study

Bisphosphonates have been used successfully in the treatment of malignant hypercalcemia and skeletal metastases. Recently, clodronate has been studied in adjuvant settings in primary breast cancer. However, long-term effect of adjuvant clodronate on bone histology has not been reported, whereas bone mineral density studies have been published. The aim of this study was to examine the effect and safety of long-term clodronate treatment on bone quality as measured by histomorphometric techniques from bone biopsies. A total of 299 patients with early stage breast cancer were randomized to receive adjuvant oral clodronate (1.6 g/day) or to a control group for 3 years. All patients had adjuvant treatment: premenopausal women had six cycles of chemotherapy and postmenopausal women had antiestrogen for 3 years. Trabecular bone quality was examined in transiliac bone biopsy specimens by using histomorphometric techniques in 28 clodronate treated and 35 control patients who were disease-free at 3 years and who allowed the biopsy specimen to be obtained. No statistically significant differences were found in the values of osteoid, mineral apposition rate, or mineralization lag time in bone biopsies between the clodronate and the control groups. Postmenopausal women who received two antiresorptive drugs, antiestrogen and clodronate, developed features of secondary hyperparathyroidism with increased eroded surface and osteoclast number. In premenopausal, women clodronate with adjuvant chemotherapy, which induced early menopause and rapid bone loss in most of the patients, seemed to conduct slight depression in bone formation. Three-year oral clodronate treatment does not impair mineralization of newly formed bone: however, clodronate with different adjuvant breast cancer treatments has a diverse impact on bone histomorphometry depending on the type of therapy.

Clodronate as a Single-dose Intravenous Infusion Effectively Provides Short-term Correction of Malignant Hypercalcemia

The efficacy and safety of a single intravenous (I.V.) infusion of clodronate 1 500 mg or 900 mg was compared with a single I.V. infusion of pamidronate 90 mg in the treatment of malignant hypercalcemia. Primary efficacy data from two separate, but parallel, randomized double-blind controlled multi-center studies (N=63), involving patients with malignant hypercalcemia (S-Cacor>2.68 mmol/l), were pooled along with results from a study (N=4), in which an open I.V. phase was followed by a randomized oral phase. The primary efficacy variable, the proportion of normocalcemic patients at day 5 could be evaluated from 51 subjects. Of them, 21 were in the clodronate 1 500 mg group, 10 in the clodronate 900 mg group and 20 in the pamidronate 90 mg group. After the rehydration, the patients were given a single I.V. infusion of clodronate 1 500 mg, clodronate 900 mg or pamidronate 90 mg. The patients were followed up for five days and S-Cacorwas measured daily. At day 5, a total of 16 patients (76%) in the clodronate 1 500 mg group, six patients (60%) in the clodronate 900 mg group and 17 patients (85%) in the pamidronate 90 mg group were normocalcemic, the differences between the treatment groups being statistically non-significant. The differences in the mean S-Cacorbetween the treatment groups were statistically non-significant. I.V. clodronate given either as 900 mg or 1 500 mg single-dose was safe and well tolerated.

Modification of serum apolipoprotein A-I, apolipoprotein B and lipoprotein(a) levels after bisphosphonates-induced acute phase response

Lipoprotein(a) (Lp(a)) is a low density lipoprotein-like particle displaying strong athero-thrombotic properties. Although the concentration of Lp(a) in plasma under strong genetic regulation, there are emerging evidences that several other factors, such as hormonal disorders, acute phase, liver and renal failure may affect its metabolism. The aim of the present study was to investigate whether bisphosphonates, an effectual drug in the treatment of malignant hypercalcemia and Paget's disease of bone, known to induce a concomitant acute phase, may have a significant influence on Lp(a) concentrations. Nine subjects (four men and five women), with plasma Lp(a) concentrations in the range between 6.4 and 17.7 mg/dl, were subjected to a single intravenous infusion of bisphosphonates (7.5 mg of aminohydroxybutylidene and 5.0 mg of aminohydroxylidene), previously dissolved in 250 ml of saline. Lp(a), apo A-I, apo B, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured at the baseline and after days one, two, four and seven. CRP, ESR and Lp(a) started to increase after two days from the treatment, reaching statistical significance after days two, four and seven, respectively. Apo B and apo A-I decreased significantly after days one and two, respectively. Apo B and apo A-I decreased significantly after days one and two, respectively. Although patterns and relative amounts of the increase of CRP were substantially different among the subjects studied, the increase of Lp(a) was more homogeneous; the peak of Lp(a) concentrations was reached only seven days after treatment in the group as a whole, in agreement with previous observations. In univariate regression analysis, significant correlations were found only between apo A-I and ESR, and apo A-I and Lp(a). The present study suggest that Lp(a) behaves as an acute phase protein. Besides, we observed a slight but significant decrease of apo A-I and apo B after administration of bisphosphonates.

Treatment of malignant hypercalcaemia with aminohexane bisphosphonate (neridronate)

Twenty patients with hypercalcaemia due to malignancy, which persisted following rehydration, were treated with the bisphosphonate, aminohexane bisphosphonate (AHBP), which is structurally similar to pamidronate. The treatment given was a single infusion of 125 mg of AHBP in 500 ml of normal saline infused over 4 h. Serum and urine biochemistry were measured before and after treatment. Acute toxicity was evaluated with particular attention to gastrointestinal symptoms, acute-phase reaction and change in renal function, as judged by serum creatinine. The infusion of AHBP induced a rapid fall apparent by day 3 (P < 0.001), with a nadir at day 7. The serum calcium remained lower at days 14 and 28 than at day 0, but the numbers followed up were low (n = 5 and n = 4). In all 20 patients there was a fall in serum calcium after treatment, and in 13 (65%) normocalcaemia was achieved. Failure to respond completely to AHBP appeared to be associated with a renal mechanism of hypercalcaemia. Treatment was associated with a significant decrease in fasting urinary calcium excretion (P < 0.05). There was no change in white cell count or renal function following AHBP and only two cases of mild pyrexia after infusion. We conclude that aminohexane bisphosphonate is an effective agent in the treatment of tumour-induced hypercalcaemia, with rapid onset of effect and low toxicity.

Newer Agents for the Treatment of MalignantHypercalcemia

The treatment of malignant hypercalcemia has involved fluids, diuretics, and specific calcium-lowering therapy with mithramycin and calcitonin. However, newer agents have recently been approved for the treatment of hypercalcemia due to malignancy. This review will discuss three such agents, gallium, etidronate, and pamidronate. This review will concentrate on the clinical pharmacologic characteristics and the clinical trials of these newer agents. Their use in the clinical practice will be suggested based on review of the published literature.

Effective treatment of malignant hypercalcaemia using a single intravenous infusion of clodronate

Effective treatment of malignant hypercalcaemia using a single intravenous infusion of clodronate

HPLC Analysis of an Amino Bisphosphonate in Pharmaceutical Formulations using Postcolumn Derivatization and Fluorescence Detection

Monosodium 4-amino-1-hydroxybutane-1, 1-diphosphonic acid (MK-217) is a bone resorption inhibitor implicated in the treatment of malignant hypercalcemia. This compound is very water soluble and has five ionizable groups with pKa values over the entire pH range. As a result, it is difficult to maintain a single species in solution for chromatographic separation. Since there is no chromophore in the molecular structure, UV detection is ineffective. The compound and its potential degradation products are separated by ion-pair chromatography using 0.01 M cetyltrimethylammonium bromide as the ion-pairing agent and a polymeric stationary phase. Detection is by fluorescence detection after postcolumn derivatization of the primary amine with ophthalaldehyde and mercaptoethanol (OPA-MERC). Optimization of the chromatographic separation and the postcolumn reaction has been carried out, and the method has been applied to the analysis of MK-217 in intravenous solutions and tablet formulations.

合成ウナギカルチトニンの血清カルシウム低下作用によく反応した舌癌患者の高カルシウム血症の１症例

Oral tumors are occassionally associated with hypercalcemia. Systemic symptoms due to hypercalcemia cause not only physical and mental troubles to patients but difficulties to physicians in choice of therapy and in prediction of prognosis since these symptoms resemble those seen at terminal stage of cancer. In the treatment of malignant hypercalcemia, simple, safe and efficient therapy that even cachectic cancer patients are able to toleate should be promptly performed.In the case reported here, a patient with tongue cancer diagnosed histologically squamous cell carcinoma, who manifested prominent hypercalcemia at a terminal stage of his clinical course was treated with synthetic eel calcitonin (Elcitonin). Administration of drug at a dosage of 160 MRCU/day intramusculary resulted in a significant decrease in serum calcium levels without notable side effects. Coadministration of glucocorticoid (Solu-Medral 250 mg/day) enhanced the effect of calcitonin.We, therefore, suggest that calcitonin with its known inhibitory action on bone resorption is one of the safest and most efficacious drugs for the treatment of hypercalcemia associated with oral cancers.

Comparative effects of 3 diphosphonates in the treatment of malignant hypercalcemia

Comparative effects of 3 diphosphonates in the treatment of malignant hypercalcemia

Treatment of malignant hypercalcaemia with clodronate.

We have assessed the effects of clodronate (dichloromethylene diphosphonate; Cl2MDP 0.8-3.2g daily by mouth for up to 3 months) in 17 episodes of hypercalcaemia and osteolysis due to carcinoma. Clodronate reduced serum calcium in 14 episodes and bone resorption in all patients. These remained suppressed for the duration of treatment, but recurred promptly when treatment was stopped. Clodronate may be a useful measure for controlling hypercalcaemia and osteolysis in patients with carcinoma.