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Erschienen in: Journal of Cancer Research and Clinical Oncology 7/2019

22.04.2019 | Original Article – Clinical Oncology

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

verfasst von: Eva Neumann, Peter Klaiber, Kathleen Freitag, Matthias Schwab, Elke Schaeffeler, Jörg Hennenlotter, Falko Fend, Stephan Kruck, Marcus Scharpf, Arnulf Stenzl, Jens Bedke, Steffen Rausch

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 7/2019

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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.
Literatur
Zurück zum Zitat Kononen J et al (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4:844–847CrossRefPubMed Kononen J et al (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4:844–847CrossRefPubMed
Zurück zum Zitat Sorich MJ, Kichenadasse G, Rowland A, Woodman RJ, Mangoni AA (2016) Angiotensin system inhibitors and survival in patients with metastatic renal cell carcinoma treated with VEGF-targeted therapy: a pooled secondary analysis of clinical trials. Int J Cancer 138:2293–2299. https://doi.org/10.1002/ijc.29972 CrossRefPubMed Sorich MJ, Kichenadasse G, Rowland A, Woodman RJ, Mangoni AA (2016) Angiotensin system inhibitors and survival in patients with metastatic renal cell carcinoma treated with VEGF-targeted therapy: a pooled secondary analysis of clinical trials. Int J Cancer 138:2293–2299. https://​doi.​org/​10.​1002/​ijc.​29972 CrossRefPubMed
Metadaten
Titel
Assessment of concomitant non-oncologic medication in patients with surgically treated renal cell carcinoma: impact on prognosis, cell-cycle progression and proliferation
verfasst von
Eva Neumann
Peter Klaiber
Kathleen Freitag
Matthias Schwab
Elke Schaeffeler
Jörg Hennenlotter
Falko Fend
Stephan Kruck
Marcus Scharpf
Arnulf Stenzl
Jens Bedke
Steffen Rausch
Publikationsdatum
22.04.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 7/2019
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-019-02914-2

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