Renal Impairment Hampers Bisphosphonate Treatment in a Quarter of Lung Cancer Patients with Bone Metastasis

Basic Clin Pharmacol Toxicol. 2017 Aug 21. doi: 10.1111/bcpt.12876. Online ahead of print.

Abstract

Renal function impairment in lung cancer patients with bone metastases was investigated, as this can limit the application of bisphosphonates representing the gold standard in the management of such cases. Clinicopathological data of 570 lung cancer patients were retrospectively analysed for changes in renal function parameters. Co-morbidities included hypertension (50%), COPD (33%) and diabetes mellitus (15%). Statistical analysis was performed with Fisher's exact tests and a Cox proportional hazards model. In patients suffering from hypertension, both median serum creatinine and blood urea nitrogen (BUN) were higher (81.9 versus 75.8 μmol/l, p<0.001 and 6.0 versus 5.7 mmol/l, p=0.005, respectively). Such a difference could not be observed in patients with diabetes. In COPD patients, only serum creatinine was higher (81.1 versus 77.3 μmol/l, p=0.004). In the whole cohort, we found that while at the time of lung cancer diagnosis the ratio of patients in the pathological range (PRR) was 8.67% for serum creatinine (median: 75 μmol/l) and 14.16% for BUN (median: 5.4 mmol/l), at the time of bone metastasis the PRR for serum creatinine increased to 16.11% (median: 77.0 μmol/l) and for BUN to 24.07% (median: 6.0 mmol/l), which is a significant increase for both parameters (p<0.001). For the whole cohort, the last laboratory results showed a 26.37% PRR for serum creatinine and 45.66% PRR for BUN (significant increase for both, p<0.001). Multivariate analysis revealed that patients with hypertension had a higher chance for switching to the pathological range sooner (p=0.033, HR: 1.372, CI: 1.025-1.835). Also, the appearance of the bone metastasis correlated with an acceleration of the onset of such a switch (p<0.001, HR: 2.655, CI: 1.581-4.456). Our results suggest that renal function is impaired in a significant proportion of lung cancer patients and highlight the importance of non-nephrotoxic drug in the management of bone metastases. This article is protected by copyright. All rights reserved.

Keywords: Lung cancer; bisphosphonate treatment; bone metastasis; renal function.