Mechanisms and treatment of hypercalcemia of malignancy

Clines, Gregory A.

doi:10.1097/med.0b013e32834b4401

Cited by 115 publications

(83 citation statements)

References 100 publications

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“…PTHrP levels have been reported to be increased in 33-84% of breast cancer and 46-47% of lung cancers (Clines, 2011). In a prospective study, Henderson et al (2006) studied 526 breast cancer patients whose PTHrP level was monitored for 10 years by using immunohistology (Henderson et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Impact of Chemotherapy on Hypercalcemia in Breast and Lung Cancer Patients

Hassan¹,

Yusoff²,

Othman³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Introduction: Hypercalcemia is mainly caused by bone resorption due to either secretion of cytokines including parathyroid hormone-related protein (PTHrP) or bone metastases. However, hypercalcemia may occur in patients with or without bone metastases. The present study aimed to describe the effect of chemotherapy treatment, regimens and doses on calcium levels among breast and lung cancer patients with hypercalcemia. Methods: We carried a review of medical records of breast and lung cancer patients hospitalized in years 2003 and 2009 at Penang General Hospital, a public tertiary care center in Penang Island, north of Malaysia. Patients with hypercalcemia (defined as a calcium level above 10.5 mg/dl) at the time of cancer diagnosis or during cancer treatment had their medical history abstracted, including presence of metastasis, chemotherapy types and doses, calcium levels throughout cancer treatment, and other co-morbidity. The mean calcium levels at first hospitalization before chemotherapy were compared with calcium levels at the end of or at the latest chemotherapy treatment. Statistical analysis was conducted using the Chi-square test for categorical data, logistic regression test for categorical variables, and Spearman correlation test, linear regression and the paired sample t tests for continuous data. Results: Of a total 1,023 of breast cancer and 814 lung cancer patients identified, 292 had hypercalcemia at first hospitalization or during cancer treatment (174 breast and 118 lung cancer patients). About a quarter of these patients had advanced stage cancers: 26.4% had mild hypercalcemia (10.5-11.9 mg/dl), 55.5% had moderate (12-12.9 mg/dl), and 18.2% severe hypercalcemia (13-13.9; 14-16 mg/dl). Chemotherapy lowered calcium levels significantly both in breast and lung cancer patients with hypercalcemia; in particular with chemotherapy type 5-flurouracil+epirubicin+cyclophosphamide (FEC) for breast cancer, and gemcitabine+cisplatin in lung cancer. Conclusion: Chemotherapy decreases calcium levels in breast and lung cancer cases with hypercalcemia at cancer diagnosis, probably by reducing PTHrP levels.

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Section: Discussionmentioning

confidence: 99%

Impact of Chemotherapy on Hypercalcemia in Breast and Lung Cancer Patients

Hassan¹,

Yusoff²,

Othman³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…PTHrP promotes the release of calcium from bone and inhibits its excretion in the kidney, causing serum calcium levels to rise. This is the fundamental mechanism of humoral hypercalcemia of malignancy (27). We propose that ovarian cancers exert an analogous but subtler effect, i.e., a "humoral high normocalcemia of malignancy."…”

Section: Discussionmentioning

confidence: 99%

Serum Calcium and Serum Albumin Are Biomarkers That Can Discriminate Malignant from Benign Pelvic Masses

Kelly

Winkler

Lentz

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Biomarkers that aid in the differential diagnosis of malignant pelvic masses from benign ones prior to surgery are needed in order to triage women with malignant masses to appropriate specialist care. Because high albumin-adjusted serum calcium predicted ovarian cancer among women without evidence of disease, we hypothesized that it might predict cancer among women with pelvic masses that were evident radiographically.Methods: We studied a cohort of 514 women with pelvic masses who underwent resection at Wake Forest University Baptist Medical Center from July 2009 through June 2013. We divided patients into a "training" set, to identify associations in the data, and a "testing" set, to confirm them. Data were obtained from medical records. A best fit model was selected using the Akaike Information Criterion.Results: Albumin-adjusted serum calcium was significantly higher in women with malignant versus benign masses

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“…Production of humoral factors by the primary tumor, such as parathyroid hormone-related protein (PTHrP), infrequent tumor production of 1, 25-(OH) 2 D and parathyroid hormone, is responsible for 80% of the MAH cases. The remaining 20% of cases is caused by osteoclast bone resorption locally induced by bone metastasis (Clines et al, 2011). Yet, sometimes, the production of PTHrP and bone lysis co-works for MAH in a patient.…”

Section: Discussionmentioning

confidence: 99%

Analysis on Survival and Prognostic Factors for Cancer Patients with Malignancy-associated Hypercalcemia

Zhang

Hu²,

Cao³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Objective: To explore the incidence, clinical characteristics, diagnosis and treatment strategies, prognosis of patients with malignancy-associated hypercalcemia (MAH). Methods: The data of 115 patients with MAH who were treated at the Medical Oncology Department of Chinese PLA General Hospital from Jan., 2001 to Dec., 2010 was retrospectively reviewed. Survival analysis was performed using the Kaplan-Meier method and the Cox proportional hazard model with statistic software SPSS 18.0. Results: The patients had blood calcium levels ranging from 2.77 to 4.87 mmol/L. Except for 9 cases who died or were discharged within 5 days after admission, all other patients recovered to normal blood calcium level after treatment with bisphosphonates or intravenous hydration and diuretics; their survival after occurrence of MAH was from 1 day to 4,051 days, and the median survival time was only 50 days. In the log-rank test, the male, renal metastasis, central nervous system symptoms and hypercalcemia occurring over 140 days after cancer diagnosis were predictors of poor survival (P=0.002, P=0.046, P=0.000, P=0.009). In the COX analysis, being male, central nervous system symptoms and hypercalcemia lasting over 140 days after cancer diagnosis were independent prognostic factors for survival time (RR=2.131, P=0.027; RR=3.054, P=0.002; RR=2.403, P=0.001). According to these factors, a score system was established to predict the patient prognosis and adjust the treatment. Conclusion: Cancer patients with MAH have an extremely poor median survival. Some independent factors indicate poor prognosis, including male gender, central nervous system symptoms and hypercalcemia lasting over 140 days after cancer diagnosis. The prognostic score can serve as a reference for MAH prognosis and treatment, worthy of further investigation.

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Mechanisms and treatment of hypercalcemia of malignancy

Abstract: Recent discoveries on mechanisms of malignancy-associated hypercalcemia highlight the critical role of the osteoclast. Bisphosphonates and other novel therapies being evaluated in clinical trial target this bone-resorbing cell type and provide effective and durable serum calcium reduction.

Cited by 115 publications

References 100 publications

Impact of Chemotherapy on Hypercalcemia in Breast and Lung Cancer Patients

Impact of Chemotherapy on Hypercalcemia in Breast and Lung Cancer Patients

Serum Calcium and Serum Albumin Are Biomarkers That Can Discriminate Malignant from Benign Pelvic Masses

Analysis on Survival and Prognostic Factors for Cancer Patients with Malignancy-associated Hypercalcemia

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