Elsevier

European Journal of Cancer

Volume 47, Issue 13, September 2011, Pages 1955-1961
European Journal of Cancer

Angiotensin system inhibitors and outcome of sunitinib treatment in patients with metastatic renal cell carcinoma: A retrospective examination

https://doi.org/10.1016/j.ejca.2011.04.019Get rights and content

Abstract

Background

Sunitinib is a standard treatment for metastatic renal cell carcinoma. Angiotensin system inhibitors, including angiotensin converting enzyme inhibitors and angiotensin II receptor blockers, are widely used in hypertension, kidney disease and heart failure. Data suggests that they may inhibit tumourigenesis.

Aims

To study the effect of angiotensin system inhibitors on sunitinib treatment outcome in metastatic renal cell carcinoma.

Methods

We performed a retrospective study of an unselected cohort of patients with metastatic renal cell carcinoma who were treated with sunitinib. Patients were divided into angiotensin system inhibitors users (group 1) and non-users (group 2). The effect of angiotensin system inhibitors on objective response, time to disease progression and overall survival, was tested with adjustment for known confounding risk factors through logistic regression model and Cox regression model.

Results

Between 2004 and 2010, 127 patients with metastatic renal cell carcinoma were treated with sunitinib, 44 group 1 and 83 group 2. The groups were balanced regarding known clinicopathologic prognostic factors. Objective response was partial response/stable disease 86% versus 72% and progressive disease 14% versus 28% (p = 0.07) in group 1 versus 2, respectively. Median progression free survival was 13 versus 6 months (HR 0.537, p = 0.0055), and median overall survival 30 versus 23 months (HR 0.688, p = 0.21), in favour of group 1.

Conclusions

Angiotensin system inhibitors may improve the outcome of sunitinib treatment in metastatic renal cell carcinoma. This should be investigated prospectively, and if validated applied in clinical practise and clinical trials.

Introduction

Renal cell carcinoma is the most common cancer of the kidney.1 Thirty percent of patients present with metastatic disease2, 3, and recurrence develops in 40% of patients treated for a localised tumour.2, 4 An understanding of the pathogenesis of renal cell carcinoma at the molecular level, and randomised clinical trials, has established the standard role of the orally administered vascular endothelial growth factor receptor and platelet derived growth factor receptor inhibitor sunitinib for the treatment of advanced renal cell carcinoma.5

Data suggests that angiotensin II, via activation of the angiotensin II type 1 receptors, stimulates cellular proliferation6 and migration,7 and induces angiogenesis by upregulating the vascular endothelial growth factor receptor.8, 9 Therefore, the angiotensin system may be implicated in the tumourigenesis process, and its blockade can represent a novel molecular targeted therapy.10, 11 Angiotensin system inhibitors, including angiotensin converting enzyme inhibitors and angiotensin II receptor blockers, are widely used in the treatment of hypertension, chronic kidney disease and heart failure. Pre-clinical and clinical studies suggested that blockade of the renin–angiotensin pathway with angiotensin system inhibitors may inhibit tumour growth in several cancer types, including reducing the incidence of advanced adenomatous colon polyps,12 retarding tumour growth and decreasing the extent of colorectal cancer liver metastases,13 triggering apoptotic cell death in human pancreatic cancer cells,14 delaying progression of pancreatic intraepithelial neoplasia and cancer,15 and increasing survival in patients with advanced non-small cell lung cancer undergoing treatment with platinum based chemotherapy.16

In the present study we sought to determine the effect of concomitant angiotensin system inhibitors use on the outcome of patients with metastatic renal cell carcinoma that are treated with sunitinib.

Section snippets

Study group

Between January 1st 2002 and November 30 2010, 379 patients with histologically confirmed metastatic renal cell carcinoma were registered and seen in the division of medical oncology, Johns Hopkins Kimmel Cancer Center. Of these, 127 patients that were treated with sunitinib, between February 1st 2004 and November 30 2010, comprised the study group. The other 252 patients were treated with therapies other than sunitinib. Data were retrospectively collected from electronic medical records and

Patient characteristics

One hundred and twenty-seven patients (age 60.7 ± 11.4 years, mean ± SD; male 71%, n = 90) with metastatic renal cell carcinoma that were treated with sunitinib between February 1st 2004 and November 30 2010. 82% of the patients (n = 104) were treated and followed with sunitinib at Johns Hopkins Kimmel Cancer Center. 18% of the patients (n = 23) were treated with sunitinib at other institutions, and came to Johns Hopkins Kimmel Cancer Center for recommendations and further treatments after progression on

Discussion

The present study suggests that concomitant use of angiotensin system inhibitors may improve the outcome of sunitinib treatment in metastatic renal cell carcinoma. In this retrospective study, patients receiving angiotensin converting enzyme inhibitors and angiotensin II receptor blockers, before or within one month of sunitinib treatment, had a a significant (HR 0.537, p = 0.0055) 7 months increase of the progression free survival, after adjustment for other known risk factors for poorer outcome.

Conflict of interest statement

None declared.

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