The hypercalcemia of malignancy: Pathogenesis and management

Mundy, Gregory R.; Martin, T. J.

doi:10.1016/0026-0495(82)90012-9

Cited by 300 publications

(100 citation statements)

References 172 publications

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“…Of these 65 patients, 57 already had advanced stage disease (Stage III and IV) at the time of their first visit. Although the frequency of TIH in our clinics is lower than what has been reported previously for lung carcinoma patients (range, 12.5-35%), 4,9 it should be noted that the current study data represent the frequency of TIH in lung carcinoma patients at the time of their first presentation.…”

Section: Tih In Lung Carcinoma Patientscontrasting

confidence: 74%

“…3 TIH progressively causes diverse clinical symptoms, such as nausea, unconsciousness, and coma, that profoundly affect the morbidity and eventual mortality of patients with cancer. 3,4 To treat and manage TIH in a timely and appropriate manner, the development of a serum marker that reliably reflects the state of TIH is very useful. It generally has been recognized that increased bone resorption is the primary cause of TIH.…”

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confidence: 99%

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Parathyroid hormone‐related protein measured at the time of first visit is an indicator of bone metastases and survival in lung carcinoma patients with hypercalcemia

Hiraki

Ueoka

Bessho

et al. 2002

Cancer

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BACKGROUNDParathyroid hormone‐related protein (PTH‐rP) is a major cause of tumor‐induced hypercalcemia (TIH) and frequently is found to be elevated in serum of patients with TIH. In the current study, the authors examined the usefulness of PTH‐rP measurement at the time of first presentation in the follow‐up of lung carcinoma patients with TIH.METHODSThe authors retrospectively studied 23 of 1149 lung carcinoma patients who were found to have TIH at the time of first presentation for the correlation between serum PTH‐rP and the development of bone metastases and survival compared with lung carcinoma patients without TIH who were matched by gender, age, Eastern Cooperative Oncology Group performance status, histological type of tumor, and stage of the disease.RESULTSTwenty‐three lung carcinoma patients with TIH demonstrated significantly increased serum levels of PTH‐rP (mean ± standard error [SE], 84.1 ± 16.5 pmol/L) compared with control patients without TIH (mean ± SE, 36.2 ± 2.0 pmol/L) at the time of first presentation, (P < 0.001). In these hypercalcemic patients, patients whose serum PTH‐rP was > 150 pmol/L (n = 16) were found to have a significantly increased rate of bone metastases (71.4% vs. 12.5%; P = 0.01) and decreased survival (median survival of 1.4 months vs. 5.4 months; P < 0.015) compared with patients whose serum PTH‐rP was < 150 pmol/L (n = 7).CONCULUSIONSThe data from the current study suggest that serum PTH‐rP as determined at the time of first presentation is a useful indicator of not only hypercalcemia but also bone metastasis and eventual survival in patients with lung carcinoma. Cancer 2002;95:1706–13. © 2002 American Cancer Society.DOI 10.1002/cncr.10828

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Section: Tih In Lung Carcinoma Patientscontrasting

confidence: 74%

mentioning

confidence: 99%

Parathyroid hormone‐related protein measured at the time of first visit is an indicator of bone metastases and survival in lung carcinoma patients with hypercalcemia

Hiraki

Ueoka

Bessho

et al. 2002

Cancer

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“…Studies from industrialised nations in the 1970s and 1980s, as well as more recent studies from other countries, report that patients with squamous-cell carcinoma (SCC) of the lung have the highest frequency of humoral hypercalcaemia of malignancy (HHM; ranging from 27 to 66%) as compared to other tumour types (Bender and Hansen, 1974;Mundy and Martin, 1982;Lazaretti-Castro et al, 1993). The precise mechanisms that activate high levels of PTHrP gene expression in tumours that are associated with HHM have yet to be identified.…”

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confidence: 99%

Inhibition of epidermal growth factor receptor signalling reduces hypercalcaemia induced by human lung squamous-cell carcinoma in athymic mice

et al. 2007

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The purpose of this study was to evaluate the role of the epidermal growth factor receptor (EGFR) in parathyroid hormone-related protein (PTHrP) expression and humoral hypercalcaemia of malignancy (HHM), using two different human squamous-cell carcinoma (SCC) xenograft models. A randomised controlled study in which nude mice with RWGT2 and HARA xenografts received either placebo or gefitinib 200 mg kg À1 for 3 days after developing HHM. Effectiveness of therapy was evaluated by measuring plasma calcium and PTHrP, urine cyclic AMP/creatinine ratios, and tumour volumes. The study end point was at 78 h. The lung SCC lines, RWGT2 and HARA, expressed high levels of PTHrP mRNA as well as abundant EGFR protein, but very little erbB2 or erbB3. Both lines expressed high transcript levels for the EGFR ligand, amphiregulin (AREG), as well as, substantially lower levels of transforming growth factor-a (TGF-a), and heparin binding-epidermal growth factor (HB-EGF) mRNA. Parathyroid hormone-related protein gene expression in both lines was reduced 40 -80% after treatment with 1 mM of EGFR tyrosine kinase inhibitor PD153035 and precipitating antibodies to AREG. Gefitinib treatment of hypercalcaemic mice with RWGT2 and HARA xenografts resulted in a significant reduction of plasma total calcium concentrations by 78 h. Autocrine AREG stimulated the EGFR and increased PTHrP gene expression in the RWGT2 and HARA lung SCC lines. Inhibition of the EGFR pathway in two human SCC models of HHM by an anilinoquinazoline demonstrated that the EGFR tyrosine kinase is a potential target for antihypercalcaemic therapy.

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“…The pathophysiology of hypercalcaemia differs depending on the tumour type, but two broad categories are recognized (Mundy and Martin, 1982). In humorally mediated hypercalcaemia, the elevation in blood calcium is most often caused by release of parathyroid hormone-related protein (PTHrP), which causes a generalized increase in osteoclastic bone resorption and increased reabsorption of calcium by the renal tubule (Yates et al, 1988;Ralston, 1987;Martin and Suva, 1989).…”

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confidence: 99%

Dose-response study of ibandronate in the treatment of cancer-associated hypercalcaemia

Ralston

Thiébaud²,

Herrmann³

et al. 1997

Br J Cancer

131

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Summary Hypercalcaemia is an important cause of morbidity in malignant disease. We studied the efficacy and safety of intravenous ibandronate (a new, potent bisphosphonate) in a multicentre study of 147 patients with severe cancer-associated hypercalcaemia which had been resistant to treatment with rehydration alone. Of 131 randomized patients who were eligible for evaluation, 45 were allocated to receive 2 mg ibandronate, 44 patients to receive 4 mg and 42 patients to receive 6 mg. Serum calcium values fell progressively in each group from day 2, reaching a nadir at day 5, and in some patients normocalcaemia was maintained for up to 36 days after treatment. The 2-mg dose was significantly less effective than the 4-mg or 6-mg dose in correcting hypercalcaemia, as the number of patients who achieved serum calcium values below 2.7 mm after treatment was 50% in the 2-mg group compared with 75.6% in the 4-mg group and 77.4% in the 6-mg group (P < 0.05; 2 mg vs others). In a logistic regression analysis, three factors were found to predict response; ibandronate dose (higher doses were more effective), severity of presenting hypercalcaemia (severe hypercalcaemia was associated with less complete response) and tumour type (patients with breast carcinoma and haematological tumours responded better than those with other tumours). Ibandronate was generally well tolerated and no serious drug-related adverse events were observed. We conclude that ibandronate is a safe, well tolerated and effective treatment for cancer-associated hypercalcaemia, which should prove a useful addition to the current range of therapies available to treat this condition.

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The hypercalcemia of malignancy: Pathogenesis and management

Cited by 300 publications

References 172 publications

Parathyroid hormone‐related protein measured at the time of first visit is an indicator of bone metastases and survival in lung carcinoma patients with hypercalcemia

Parathyroid hormone‐related protein measured at the time of first visit is an indicator of bone metastases and survival in lung carcinoma patients with hypercalcemia

Inhibition of epidermal growth factor receptor signalling reduces hypercalcaemia induced by human lung squamous-cell carcinoma in athymic mice

Dose-response study of ibandronate in the treatment of cancer-associated hypercalcaemia

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