Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
CORRESPONDENCE
Year : 2018  |  Volume : 14  |  Issue : 12  |  Page : 1223-1226

Symptomatic treatment of brain metastases in renal cell carcinoma with sorafenib


Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan 250012, China

Date of Web Publication11-Dec-2018

Correspondence Address:
Xiuwen Wang
Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan 250012
China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.189402

Rights and Permissions
 > Abstract 


Brain metastasis is synchronous to the diagnosis of renal cell carcinoma (RCC). The prognosis of brain metastasis in RCC with the current treatment options is dismissal. Therefore, we present a case of an elderly female patient with RCC showing a partial response of brain metastasis after 18 months of 600 mg once daily sorafenib treatment who underwent right-sided nephrectomy. Further, withdrawal of sorafenib resulted in psychiatric changes along with increased metastasis lesions, which were recovered upon resuming the treatment, proposing that oral sorafenib can be used safely and efficiently for treatment of brain metastasis in advanced RCC.

Keywords: Brain metastasis, renal cell carcinoma, sorafenib


How to cite this article:
Hu D, Hu Y, Li J, Wang X. Symptomatic treatment of brain metastases in renal cell carcinoma with sorafenib. J Can Res Ther 2018;14, Suppl S5:1223-6

How to cite this URL:
Hu D, Hu Y, Li J, Wang X. Symptomatic treatment of brain metastases in renal cell carcinoma with sorafenib. J Can Res Ther [serial online] 2018 [cited 2019 Sep 20];14:1223-6. Available from: http://www.cancerjournal.net/text.asp?2018/14/12/1223/189402




 > Introduction Top


Development of brain metastases is a common and significant problem in patients with renal cell carcinoma (RCC), with a reported incidence of approximately 4–7%. RCC patients with brain metastases exhibit poor prognosis with median overall survival of only 11 months from diagnosis.[1] Owing to the poor prognosis, these patients are generally excluded from the clinical trials for RCC,[2] but clinical data are required to evaluate therapeutic approaches, especially for geriatric population.

RCC is a chemoresistant hypervascularized tumor, frequently associated with upregulated activity of angiogenic promoters such as vascular endothelial growth factor (VEGF).[3] Therefore, VEGF inhibitors such as bevacizumab, sorafenib, and sunitinib have been used in RCC. Among them, sorafenib (Nexavar®; Bayer Healthcare Pharmaceuticals, Wayne, NJ and Onyx Pharmaceuticals, Inc., Emeryville, CA, USA) is an orally bioavailable multitargeted tyrosine kinase inhibitor (TKI), with potential antiangiogenic and antiproliferative properties. Based on the promising results observed in clinical trials, it received widespread regulatory approval for the treatment of advanced RCC.[4] Furthermore, there are a few studies that report the efficacy of sorafenib in the treatment of RCC patients with brain metastases.[5],[6] Hence, more studies are warranted to establish the effectiveness of sorafenib treatment in RCC patients with brain metastases and in those with relapse of brain metastases after withdrawal of the therapy. This case report details the partial response (PR) of brain metastasis after 12 months of sorafenib treatment in an elderly Chinese female patient with RCC.


 > Case Report Top


In October 29, 2007, histopathological analysis of a 75-year-old Chinese female nephrectomized kidney revealed right renal clear cell carcinoma with a cutting area of 6.5 cm × 5.5 cm (tumor node metastasis classification: T1bN0M0, Stage I), without apparent presence of cancer cells on the ureteral stump or perirenal metastasis of the lymph nodes. The patient was put on immunotherapy for the next 2 months.

Subsequent chest computed tomography (CT) scans revealed metastases in the lungs [Figure 1]. Once daily, 600 mg oral sorafenib treatment led to attainment of PR. However, she developed Grade 2 hand-foot syndrome and fatigue. After 2 months of treatment, a chest CT scan was performed, which revealed a significant shrinkage of lung metastases [Figure 1]b. Although the chest CT scan revealed Grade 4 hepatotoxicity, the patient's liver function recovered after symptomatic treatment for 2 months, during which she took sorafenib inconsistently.
Figure 1: (a and b) Computed tomography chest showing metastasis in the lungs. (a) Before treatment on October 30, 2009; (b) after 2 months of treatment on February 1, 2010

Click here to view


Withdrawal of sorafenib after 6 months prominently increased lung metastasis lesions both in amount and size. The largest lesion reported was 4.5 cm × 3.8 cm × 2.1 cm in the right side of the lung [Figure 2]a. Brain CT scan showed an irregular mixed-density lesion in the left frontal lobe with unclear boundary. An acupressure-like low-density area was detected around the lesion and the adjacent sulci disappeared. The anterior horn of lateral ventricle and left lateral cistern shrunk by pressure while the brain midline structure slightly shifted to the right [Figure 3] and [Figure 4]. Whole-brain radiation therapy was not possible in this patient because of the presence of severe psychiatric symptoms.
Figure 2: (a and b) Computed tomography chest showing metastasis in the lungs. (a) Before treatment on April 28, 2011; (b) after 6 weeks of treatment on June 8, 2011

Click here to view
Figure 3: Brain computed tomography comparing posttreatment with pretreatment cerebral metastasis

Click here to view
Figure 4: Brain computed tomography comparing posttreatment with pretreatment cerebral edema

Click here to view


After 12 months, the patient was restarted on oral sorafenib combined with sedation and dehydration for 1 week. A chest CT scan revealed dramatic improvement in regression of the lung lesions by >50% compared with the lesions observed before restarting the therapy, with treatment efficacy reaching PR [Figure 2]b. The dosage of sorafenib was reduced and adjusted to 400 mg twice daily after routine follow-ups. After 6 weeks of treatment with sorafenib monotherapy, notable improvements occurred in the patient's clinical status. The psychiatric syndrome was relieved, cerebral metastasis was stable [Figure 3], and the cerebral edema extenuated [Figure 4]. All these observations were sustained for 18 months until the patient died as a consequence of disease progression to the chest and abdomen.


 > Discussion Top


RCC is the most common type of renal cancer. Of which, metastatic RCC is resistant to chemotherapy and usually treated by immunotherapy. However, immunotherapy is usually associated with potential toxicities.[7] The promising efficacy and tolerability data obtained from a few of the studies demonstrated that molecular-targeted therapies, especially receptor TKIs, may be an effective therapeutic strategy along with surgery, radiotherapy, or palliative therapy in RCC patients with significantly lower brain metastasis.[8] With the advent of molecular-targeted therapies over the past few years, there has been a drastic change in the therapeutic landscape of RCC.

Sorafenib is a small-molecule inhibitor of multiple protein kinases that are components of signaling pathways controlling tumor growth and angiogenesis.[4] There is also evidence on the inhibitory effect of sorafenib on brain metastasis and natural course of disease in RCC patients.[7]

Meanwhile, the inhibitory effect of sorafenib on brain metastasis of RCC has been confirmed by the retrospective analysis of phase III randomized Treatment Approaches in Renal Cancer Global Evaluation Trials trial.[9] A subgroup analysis on 1031 cases of RCC in the European expanded trial (European Advanced Renal Cell Carcinoma Sorafenib) demonstrated a control rate of 60.7% and a median PFS of 7.4 months for brain metastasized RCC.[10] In our case, a chest CT scan after 2 months of sorafenib treatment indicated regression in lung lesions by >50% and attainment of PR. On the contrary, discontinuation of sorafenib treatment significantly increased the size and amount of lung lesions and resulted in relapse of brain metastasis, resuming the treatment relieved clinical symptoms and lung lesions reduced by >50% compared with pretreatment lung metastases, and PR was achieved. In addition, brain CT scan showed that cerebral edema was mitigated and brain metastasis reached stable disease, which lasted for 18 months until the patient died on November 29, 2012, due to progression of the disease to the chest and abdomen. Oral sorafenib treatment was effective in controlling the lesions for 18 months without performing whole-brain radiotherapy, and the adverse effects were well tolerated. However, further research is needed to establish the role of sorafenib in the treatment of brain metastases from RCC. Moreover, if critical targets of therapeutic value in the RCC cell signal transduction pathways can be explored, performing a corresponding genetic testing before treatment will contribute greatly to the choice of treatment and assessment of prognosis.

Acknowledgments

The authors were supported by grants from Youth Foundation of Qilu Hospital of Shandong University (No. 26010175616104). We thank Dr. Amit Bhat and Mrs. Nishi Gupta (Indegene Lifesystems Pvt Ltd, Bangalore) for providing medical writing services on behalf of Bayer Healthcare Co Ltd., Beijing 100176, P. R. China.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Doh LS, Amato RJ, Paulino AC, Teh BS. Radiation therapy in the management of brain metastases from renal cell carcinoma. Oncology (Williston Park) 2006;20:603-13.  Back to cited text no. 1
    
2.
Flanigan RC, Campbell SC, Clark JI, Picken MM. Metastatic renal cell carcinoma. Curr Treat Options Oncol 2003;4:385-90.  Back to cited text no. 2
    
3.
Renal Cell Carcinoma. MedlinePlus Web Site, 2014. Available from: http://www.nlm.nih.gov/medlineplus/ency/article/000516.html. [Last accessed on 2015 Jul 24].  Back to cited text no. 3
    
4.
Jäger D, Ma JH, Mardiak J, Ye DW, Korbenfeld E, Zemanova M, et al. Sorafenib treatment of advanced renal cell carcinoma patients in daily practice: The large international PREDICT study. Clin Genitourin Cancer 2015;13:156-64.e1.  Back to cited text no. 4
    
5.
Walid MS, Johnston KW. Successful treatment of a brain-metastasized renal cell carcinoma. Ger Med Sci 2009;7:Doc28.  Back to cited text no. 5
    
6.
Helgason HH, Mallo HA, Droogendijk H, Haanen JG, van der Veldt AA, van den Eertwegh AJ, et al. Brain metastases in patients with renal cell cancer receiving new targeted treatment. J Clin Oncol 2008;26:152-4.  Back to cited text no. 6
    
7.
Fyfe G, Fisher RI, Rosenberg SA, Sznol M, Parkinson DR, Louie AC. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol 1995;13:688-96.  Back to cited text no. 7
    
8.
Verma J, Jonasch E, Allen P, Tannir N, Mahajan A. Impact of tyrosine kinase inhibitors on the incidence of brain metastasis in metastatic renal cell carcinoma. Cancer 2011;117:4958-65.  Back to cited text no. 8
    
9.
Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007;356:125-34.  Back to cited text no. 9
    
10.
Beck J, Procopio G, Bajetta E, Keilholz U, Negrier S, Szczylik C, et al. Final results of the European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study: A large open-label study in diverse community settings. Ann Oncol 2011;22:1812-23.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

Top
 
 
  Search
 
Similar in PUBMED
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  >Abstract>Introduction>Case Report>Discussion>Article Figures
  In this article
>References

 Article Access Statistics
    Viewed1283    
    Printed77    
    Emailed0    
    PDF Downloaded78    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]