, Volume 28, Issue 3, pp 311-317
Date: 05 May 2010

Treatment with tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma is associated with drug-induced hyperparathyroidism: a single center experience in 59 patients

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Abstract

Purpose

Multi-targeted tyrosine kinase inhibitors (MTKIs) are the standard in the treatment of metastatic renal cell carcinoma (mRCC). In spite their clinical activity, interaction with physiological functions has been shown. Here, we report on alterations of the bone mineral metabolism in patients with mRCC treated with MTKIs.

Methods

Fifty-nine patients with mRCC treated during April 2005 and September 2009 at our center were evaluated. Demographics, chemistry, parathyroid and renal function, bone metastasis and clinics were assessed, retrospectively. Parathyroid hormone (PTH), calcium and phosphate were either determined prior to, during or after cessation of MTKI therapy.

Results

From evaluable patients, 90% (N = 53) received at least one MTKI treatment, 10% (N = 8) had evaluations without MTKI exposure. The mean PTH value prior to MTKI treatment was 49.4 (range (r):2.5–115), increased during the therapy to 121.2 (r:5–302) (P = 0.003) and returned to its basic values after MTKI cessation. In parallel, mean phosphate significantly decreased during the treatment from 1.10 (r = 0.66–1.59) to 0.87 (r = 0.48–1.45) (P < 0.001) and calcium showed a slight decrease (P = 0.039). PTH alterations were associated with clinical signs in some patients but not with bone metastasis or renal function. Univariate logistic regression analysis of pathologically elevated PTH levels revealed an association with MTKI treatment duration.

Conclusion

Even though the mechanism of bone mineral alteration remains elusive, the MTKI treatment is associated with a dysregulated parathyroid axis, which may have clinical implications in a number of patients. Furthermore, prospective trials are mandatory, and PTH monitoring should be considered in selected patients during MTKI treatment.