|Year : 2018 | Volume
| Issue : 12 | Page : 1223-1226
Symptomatic treatment of brain metastases in renal cell carcinoma with sorafenib
Dongyan Hu, Yu Hu, Jisheng Li, Xiuwen Wang
Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan 250012, China
|Date of Web Publication||11-Dec-2018|
Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan 250012
Source of Support: None, Conflict of Interest: None
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
| > Introduction|| |
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. Owing to the poor prognosis, these patients are generally excluded from the clinical trials for RCC, 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). 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. Furthermore, there are a few studies that report the efficacy of sorafenib in the treatment of RCC patients with brain metastases., 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|| |
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|
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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|
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|Figure 3: Brain computed tomography comparing posttreatment with pretreatment cerebral metastasis|
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|Figure 4: Brain computed tomography comparing posttreatment with pretreatment cerebral edema|
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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|| |
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. 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. 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. There is also evidence on the inhibitory effect of sorafenib on brain metastasis and natural course of disease in RCC patients.
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. 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. 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.
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
Conflicts of interest
There are no conflicts of interest.
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