Impact of Chemotherapy on Hypercalcemia in Breast and Lung Cancer Patients

  • Hassan, Bassam Abdul Rasool (Clinical Pharmacy Discipline, School of Pharmaceutical Sciences, University Sains Malaysia) ;
  • Yusoff, Zuraidah Binti Mohd (Clinical Pharmacy Discipline, School of Pharmaceutical Sciences, University Sains Malaysia) ;
  • Hassali, Mohamed Azmi (Discipline of Social and Administrative Pharmacy, School of Pharmaceutical Sciences, University Sains Malaysia) ;
  • Othman, Saad Bin (Clinical Pharmacy Discipline, School of Pharmaceutical Sciences, University Sains Malaysia) ;
  • Weiderpass, Elisabete (Department of Epidemiology and Biostatistics, Karolinksa Institutet)
  • Published : 2012.09.30


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.


  1. Clines G (2011). Mechanisms and treatment of hypercalcemia of malignancy. Current Opinion Endocrinology, Diabetes and Obesity, 18, 339-46.
  2. Dolan S (2005). Electrolyte abnormalities in 'The royal marsden hospital handbook of cancer chemotherapy', Eds Brighton D, Wood M, Elsevier, Churchill Livingstone, pp 205-08.
  3. Drug Lib.COM (2010). Study of Denosumab in the Treatment of Hypercalcemia of Malignancy in Subjects With Elevated Serum Calcium in 'Information Source: Amgen Information Obtained From Clinicaltrials', Eds. Gov on October 04. New York, Drug; 2010.
  4. Ericson K. Hypercalcemia (1999) in 'Gale encyclopedia of medicine', Eds Olendorf D, Jeryan C, Boyaden K. Gale Research, An International Thomson company, Farmington Hills, pp 1500-3.
  5. Hartley S, Repaskey W, Rohde J (2012). What Is the Best Treatment of an Adult Patient with Hypercalcemia of Malignancy. Journal [serial on the Internet]. Date; July. 2012.
  6. He Z, Naik SG, Rathnasabapathy C, et al (2008). Hypercalcemia of malignancy in the era of zolendronic acid and effective chemotherapy. J Clin Oncol, 26, 15.
  7. Helft PR, Rudin CM (1999). Metabolic and electrolyte complications of malignancy. in 'Oncologic Therapies', Eds Vokes EE, Golomb HM, Springer-Verlag, Berlin Heidelberg, Chicago pp 244-257.
  8. Henderson MA, Danks JA, Slavin JL, et al (2006). Parathyroid hormone-related protein localization in breast cancers predict improved prognosis, Cancer Research, 66, 2250-6.
  9. Kanbay M, Huddam B, Guyener N, Bovaciolu S (2009). Metastatic Medulloblastoma Presented with Hypercalcemia, A Rare Case. The Internet Journal of Oncology, 13, 47.
  10. Kelland LR. Cancer cell biology, drug action and resistance in 'The Royal Marsden Hospital Handbook of Cancer Chemotherapy', Eds. Brighton D, Wood M. Elsevier / Churchill Livingstone, London, 47.
  11. Medicine net. Com. Chemotherapy and Cancer Treatment, Coping with Side Effects (2010). New York, Medicine net. Com. 2010. asp?articlekey=21716
  12. Mundy GR (1990). Calcuim homeostasis: Hypercalcemia and hypocalcemia/General concepts of calcuim homeostasis. Cambridge. The University Press.
  13. National Cancer Institute NCI (2010). Hypercalcemia, managment. New York: National Cancer Institute NCI, [updated 2010; cited]; Available from: http://www.cancer. gov/cancertopics/pdq/supportivecare/hypercalcemia/ HealthProfessional/page5. 2010.
  14. Oda N, Nakai A, Hayashi R, et al, (1998). Utility of measuring serum parathyroid hormone-related protein concentration in leukemic patients with hypercalcemia for assessing disease status. Eur J Endocrinol, 139, 323-9.
  15. Swartout-corbeil D (2002). Hypercalcemia in 'Gale encyclopedia of cancer', Ed Thackery E. Gale group, Detroit, pp 516-518.
  16. Swartout-corbeil D (2005). Hypercalcemia in 'Gale encyclopedia of cancer 2', Ed Longe JL. Gale group, Detroit, pp 579-581.
  17. Tannehill-gregg S, Levine A, Nadella M (2006). The effect of zoledronic acid and osteoprotegerin on growth of human lung cancer in the tibias of nude mice. Clinical and Experimental Metastasis, 23, 19-31.
  18. Tovar Sepulveda VA, Shen X, Falzon M (2002). Intracrine PTHrP Protects against Serum Starvation-Induced Apoptosis and Regulates the Cell Cycle in MCF-7 Breast Cancer Cells. Endocrinology , 143, 596.
  19. Unal S, Durmaz E, Erkoçoğlu M, et al (2008). The rapid correction of hypercalcemia at presentation of acute lymphoblastic leukemia using high-dose methylprednisolone. Turkish J Pediatrics, 50, 171-5.
  20. World Health Organization (2010). Study of Denosumab in the Treatment of Hypercalcemia of Malignancy in Subjects with Elevated Serum Calcium in 'Amgen Call Center', Eds. Italy, World Health Organization; 2010.
  21. Wysolmerski JJ, Broadus AE (1994). Hypercalcemia of malignancy: The central role of parathyroid hormone-related protein. Ann Rev Med, 45, 189-200.

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