Calcium and phosphorus disorders

Disturbances in calcium and phosphorus homeostasis are commonly encountered when caring for cancer patients. These may result from the malignancy itself or as a complication of treatment. A thorough understanding of pathophysiologic processes, whereby the tumor or its therapy result in abnormalities of calcium and phosphorus balance, is essential to managing cancer patients. Disturbances resulting in hypercalcemia can be divided into four types: tumor production of parathyroid hormone related peptide (PTHrP) known as humoral hypercalcemia of malignancy (HHM), local osteolytic hypercalcemia mediated by cytokine production most commonly seen in multiple myeloma or breast cancer, calcitriol production, and ectopic parathyroid hormone secretion. HHM makes up 80% of cancer-related hypercalcemia. The most common solid organ malignancies are squamous cell carcinomas most frequently from lung, head and neck, and skin. Adult T-cell leukemia/lymphoma cells also produce PTHrP. Lymphomas, leukemias and gastrointestinal stromal tumors result in hypercalcemia from calcitriol production. Hypocalcemia can occur with osteoblastic metastases, tumor lysis syndrome, hypomagnesemia, cisplatin, axitinib, 5-fluorouracil with low dose leucovorin, estramustine, nab-paclitaxel, high dose interleukin 2 and agents used to treat hypercalcemia, such as bisphosphonates and denosumab. Tumor lysis syndrome whether from treatment or spontaneous can lead to hyperphosphatemia and is the most common oncologic emergency. Prophylaxis with fluids, allopurinol or rasburicase is important to reduce risk of acute kidney injury. Hypophosphatemia can be caused by tumor production of fibroblast growth factor-23; and Fanconi syndrome from medications, lymphoma or multiple myeloma. Other drugs used to treat cancers may also lower serum phosphorus concentration including: BCR-ABL tyrosine kinase inhibitors, anaplastic lymphoma kinase (ALK) inhibitors, eribulin, high-dose estrogens, and mammalian target of rapamycin (mTOR) inhibitors.