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J Cancer Res Clin Oncol. 2019 Jul;145(7):1835-1843. doi: 10.1007/s00432-019-02914-2. Epub 2019 Apr 22.

Assessment of concomitant non-oncologic medication in patients with surgically treated renal cell carcinoma: impact on prognosis, cell-cycle progression and proliferation.

Author information

1
Department of Urology, Eberhard Karls University, Hoppe-Seyler- Strasse 3, 72076, Tuebingen, Germany.
2
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
3
Department of Clinical Pharmacology, Eberhard Karls University, Tuebingen, Germany.
4
Department of Pharmacy and Biochemistry, Eberhard Karls University, Tuebingen, Germany.
5
Department of Pathology, Eberhard Karls University, Tuebingen, Germany.
6
Department of Urology, Eberhard Karls University, Hoppe-Seyler- Strasse 3, 72076, Tuebingen, Germany. steffen.rausch@med.uni-tuebingen.de.

Abstract

INTRODUCTION:

Based on the observation of beneficial effects on cancer metabolism, microenvironment, or VEGF-signaling, several non-anticancer drugs have been discussed as useful in renal cell carcinoma (RCC). In the present study, we investigated the prognostic impact of concomitant medication in RCC and correlated comedication with cell-cycle and proliferation activity in corresponding surgical specimen.

METHODS:

A total of 388 patients who underwent surgery for localized RCC were included. The individual medication was evaluated according to substance classes. Tissue microarrays from corresponding tumor specimen were immunohistochemically (IHC) stained for Cyclin D1 and Ki67 and semi-quantitatively evaluated. Uni- and multivariate analyses were used to compare survival outcomes. For the comparison of IHC expression according to medication subgroups, Kruskal-Wallis analysis was performed.

RESULTS:

Median follow-up was 57.93 months (95% CI 53.27-69.43) and median OS accounted for 181.12 months (129.72-237.17). Univariate analysis identified pathological standard variables (T-stage > T2, Grading > G2, L1, N1, M1, sarcomatoid subtype, necrosis) as significant determinants of OS. Moreover, statin use (p = 0.009) and sartan use (p = 0.032) were significantly associated with improved OS. Multivariate analysis identified M1-stage (p < 0.001), statin and sartan use (p = 0.003 and p = 0.033, respectively) as independent prognosticators of survival. Expression of Ki67 was significantly reduced in patients with statin use (p = 0.013), while Cyclin D1 expression showed no correlation with comedication.

CONCLUSIONS:

Concomitant intake of statins and sartans identifies as an independent predictor of OS in RCC, and reduced Ki67 expression was significantly associated with statin use. Further evaluation of drug repurposing approaches with these substances in RCC appear warranted.

KEYWORDS:

Angiotensin receptor blockers; Cell cycle; Clear cell; Concomitant medication; Cyclin D1; HGM-CoA reductase inhibitor; Ki67; Localized; Nephrectomy; Nephron sparing surgery; Proliferation marker; Renal cell carcinoma; Sartan; Statin

PMID:
31006846
DOI:
10.1007/s00432-019-02914-2
[Indexed for MEDLINE]

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