Clinical Case 86: Answers and Summary

Which one of the following chemotherapy agents cause solitary hypophosphatemia?(select more than 1)

cisplatin	7 (38%)
sorafenib	2 (11%)
imatinib	7 (38%)
lenalidomide	4 (22%)

While many chemotherapy agents cause electrolyte disorders, hypophosphatemia is a rare occurrence.

Let’s take each chemotherapy agent at a time that is listed above.

Cisplatin classically is known to cause AKI and proximal tubular damage and hypomagnesemia but sole hypophosphatemia is rarely reported. Usually, a classic Fanconi syndrome has been described. 
So, choice A is less likely to cause solitary hypophosphatemia.

Sorafenib, a multikinase inhibitor targeting the c-Kit, RAF, VEGF and PDGF pathways, is approved for the treatment of patients with hepatocellular carcinoma and renal cell carcinoma, with a broad spectrum of activity also including selected sarcoma subtypes, thyroid cancers and melanoma. Sorafenib induces pancreatic exocrine dysfunction, leading to vitamin D malabsorption and secondary hyperparathyroidism. Patients receiving sorafenib can develop hypophosphatemia and vitamin D deficiency.

Of the 4 listed above, imatinib has been most well described with this electrolyte disorder. In NEJM, Berman and colleagues reported their findings regarding the development of hypophosphatemia and associated changes in bone and mineral metabolism in patients with either chronic myelogenous leukemia or gastrointestinal stromal tumors who are taking imatinib. A nice review article discusses the effect of all tyrosine kinase inhibitors such as imatinib and sorafenib and their effects on bone health. By inhibiting platelet-derived growth factor receptors expressed on osteoclasts, these agents cause a subsequent decrease in bone resorption and decreased calcium and phosphate egress from the bone. As a result, PTH levels increase and phosphaturia follows.

Lenalidomide and hypophosphatemia has been described in conjunction with other therapies and sole effect. It appears to be a potential renal loss mechanism. It is hard in this drug as myeloma is the primary cancer and the cancer itself can cause this electrolyte disorder. A Fanconi syndrome has also been described.