Treatment of Hemodialyzed Patients with Sunitinib in Renal Cell Carcinoma

Park, Silvia; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Kang, Won Ki; Park, Young Suk; Cho, Jin Hyun; Lim, Ho Yeong

doi:10.1159/000321033

Cited by 18 publications

(11 citation statements)

References 52 publications

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“…In the past, cytokine regimens with interferon (IFN) α-2a and interleukin-2 have been the primary treatment for mRCC. However, newly developed targeted agents have recently replaced the cytokine regimen in the initial treatment for advanced RCC [1,2]. Currently, six targeted agents have been approved for the treatment of mRCC, all of which showed efficacy and tolerable safety in large phase III clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Comparative Efficacy of Sunitinib versus Sorafenib as First-Line Treatment for Patients with Metastatic Renal Cell Carcinoma

Park

Lee²,

Park³

et al. 2012

Chemotherapy

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Background: This study investigated the efficacy and toxicity of sorafenib and sunitinib as primary treatment for patients with metastatic renal cell carcinoma (mRCC). Methods: We identified 49 and 220 patients treated with sorafenib and sunitinib, respectively, as first-line therapy in the Asan Medical Centre from April 2005 to March 2011. Results: Disease control rates of 71 and 74% were achieved with sorafenib and sunitinib, respectively (p = 0.687). After a median follow-up of 27.6 months, progression-free survival (PFS) and overall survival (OS) were not significantly different between the sorafenib and the sunitinib group (PFS 8.6 vs. 9.9 months, respectively, p = 0.948, and OS 25.7 vs. 22.6 months, p = 0.774). Patients treated with sorafenib required dose reduction due to toxicities less frequently than those treated with sunitinib (37 vs. 54%, p = 0.034). Haematological toxicity of grade 3 or 4 was more common in the sunitinib group than in the sorafenib group (45 vs. 4%, p < 0.001). Multivariate analysis showed old age, Heng's risk group, and bone and liver metastases, but not the type of vascular endothelial growth factor tyrosine kinase inhibitor, were independent prognostic factors affecting OS. Conclusion: The results of this study indicate that sorafenib has comparable efficacy to sunitinib in the treatment of mRCC patients and fewer and less severe toxicities, but the number of patients included in the study was small.

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Section: Introductionmentioning

confidence: 99%

Comparative Efficacy of Sunitinib versus Sorafenib as First-Line Treatment for Patients with Metastatic Renal Cell Carcinoma

Park

Lee²,

Park³

et al. 2012

Chemotherapy

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“…Although the prevalence of RCC among patients with hemodialysis is 40–100 times higher than the general population,18 the use of sunitinib in dialysis patients is poorly described. Studies based on the limited number of patients seem to suggest that concomitant use of sunitinib and dialysis is feasible with good results 19–21. Furthermore, it was suggested that hemodialysis did not significantly alter plasma concentrations of sunitinib 22–24.…”

Section: Discussionmentioning

confidence: 99%

The world of targeted therapies in kidney cancers: pitfalls, tips and tricks

Vallard

Trone

Langrand-Escure

et al. 2017

OTT

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In the past few years, metastatic renal cell carcinoma prognosis was improved by the development of molecular targeted therapies (TTs). At the metastatic stage, the tolerance to treatment is a major concern, not only because of the challenge of the efficacy/toxicity ratio improvement but also because of the importance of an optimal adherence to oral treatments. The present case series relates the issues of dealing with uncommon and sometimes never described side effects of sunitinib and sorafenib. The first case report deals with grade 3 vomiting during hemodialysis with concurrent administration of sunitinib. The second case is an iterative gout attack induced by sunitinib. The third case presents a grade 3 scalp dysesthesia with sorafenib. The fourth case includes an astonishing efficacy of metronomic (ie, low doses during a long period of time) bevacizumab in monotherapy. Multidisciplinary management and systematic reporting of unexpected efficacies and toxicities are needed to better understand TTs real therapeutic index. Although TTs revolutionized metastatic renal cell cancer prognosis, they also brought about previously unknown side effects. Identification and management of these off-target effects may be tricky, and therefore, comedication must be wisely chosen. As the physiopathology of these side effects is still unclear, multidisciplinary management and systematic reporting of toxicities are essential.

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“…In the past, cytokine regimens with interferon-α 2a and interleukin-2 have been the primary treatment for metastatic RCC. However, newly developed targeted agents have recently replaced the cytokine regimen in the initial treatment for advanced RCC [4,5,6]. Pazopanib was approved by the US Food and Drug Administration in October 2009 and by the European Medicines Agency in June 2010 for the treatment of metastatic RCC.…”

Section: Introductionmentioning

confidence: 99%

Pazopanib-Induced Hepatotoxicity in an Experimental Rat Model

et al. 2018

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Pazopanib is an effective treatment for advanced renal cell carcinoma and soft tissue sarcoma. Besides classical adverse events of this drug class, hepatotoxicity has been described as a frequent side effect. The aim of the present study was to evaluate the effect of pazopanib on the liver in an experimental rat model. Sixteen Wistar albino rats were divided into 3 groups: experimental toxicity was induced with pazopanib (10 mg/kg) administered for 28 days (group 2) or 56 days (group 3) orally by gavage. Group 1 (control group) received only distilled water. Rats in groups 2 and 3 were sacrificed after the collection of blood and tissue samples on the 28th and 56th days, respectively. We found significant differences in bilirubin, alkaline phosphatase, lactate dehydrogenase, glucose, triglyceride, very-low-density lipoprotein, and iron values (p < 0.050 for all) but none in any other parameter (p > 0.050). All rats in the control group had normal histological features; however, none of the rats in groups 2 and 3 showed normal histology. In group 2, we observed mild sinusoidal dilatation, congestion, enlarged Kupffer cells, accumulation of yellow-brown-black pigment in the Kupffer cells and the accumulation of hemosiderin with Prussian blue reaction in the hepatocytes. In group 3, the findings mentioned above were more prominent, and besides these findings focal acinar transformation and macrovesicular steatosis were also observed. In group 3, mild inflammation within the portal areas was observed consisting of lymphocytes, neutrophils, and eosinophils. This study is the first that reports the biochemical and histopathological evaluation of pazopanib-related hepatic toxicity.

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Treatment of Hemodialyzed Patients with Sunitinib in Renal Cell Carcinoma

Cited by 18 publications

References 52 publications

Comparative Efficacy of Sunitinib versus Sorafenib as First-Line Treatment for Patients with Metastatic Renal Cell Carcinoma

Comparative Efficacy of Sunitinib versus Sorafenib as First-Line Treatment for Patients with Metastatic Renal Cell Carcinoma

The world of targeted therapies in kidney cancers: pitfalls, tips and tricks

Pazopanib-Induced Hepatotoxicity in an Experimental Rat Model

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