Efficacy and safety of axitinib for metastatic renal cell carcinoma in patients on hemodialysis for end‐stage renal disease: Case series of eight patients

Ishihara, Hiroki; Takagi, Toshio; Kondo, Tsunenori; Yoshida, Kazuhiko; Okumi, Masayoshi; Tanabe, Kazunari

doi:10.1111/iju.14093

Cited by 9 publications

(3 citation statements)

References 8 publications

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“…The median PFS of 10.9 and 9 months and OS of 18.4 and 12.5 months presented in expanded-access trials of sunitinib and sorafenib, respectively [ 54 , 55 ], are comparable to those reported in HD patients (Table 3 ). Evidence from a small number of cases also suggests a good efficacy and tolerability of pazopanib and axitinib treatment in mRCC patients undergoing dialysis [ 56 , 57 ]. At this time, there are no established evidence-based guidelines on the management of such patients.…”

Section: Renal Toxicities Of Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Renal toxicity of targeted therapies for renal cell carcinoma in patients with normal and impaired kidney function

Mielczarek

Brodziak

Sobczuk

et al. 2021

Cancer Chemother Pharmacol

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The introduction of novel targeted therapies during the last 2 decades has led to a significant improvement in patients' clinical outcomes with renal cell carcinoma. However, this improvement came at the price of a whole new spectrum of adverse events, including renal toxicity. Systemic treatment of patients with kidney neoplasms who often present with impairment of kidney function, even prior to treatment, poses an increasing diagnostic and therapeutic challenge for clinicians. Common lifestyle-related comorbidities, i.e., hypertension and diabetes, may contribute to further impairment of kidney function. The lack of official guidelines and the exclusion of patients with reduced kidney function from the clinical trials of recently approved drugs complicate the issue even further. Early detection and correct management of renal toxic effects are crucial to preserve kidney function and ensure the optimal administration of life-prolonging therapies. This review presents detailed information on the renal toxicities of three groups of drugs commonly used in renal cell carcinoma treatment: tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and immune checkpoint inhibitors. We outline the incidence and underlying mechanisms of renal adverse effects with a focus on patients on renal replacement therapy, as well as present suggestions for their management.

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Section: Renal Toxicities Of Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Renal toxicity of targeted therapies for renal cell carcinoma in patients with normal and impaired kidney function

Mielczarek

Brodziak

Sobczuk

et al. 2021

Cancer Chemother Pharmacol

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“…According to previous reports regarding the safety and efficacy of each single use of pembrolizumab or axitinib for patients on HD, each drug could be used for them at the same dosage as patients with normal renal function because the amount of each drug removed by the dialyzer was found to be small enough that the influence of HD could be ignored. Thiery et al [ 4 ], Kopecky et al [ 5 ], and Ishihara et al [ 6 ] reported the efficacy and safety of normal use of axitinib in patients with ESRD. Although axitinib has a small molecular weight, it is not removed by dialysis because it binds to proteins such as albumin.…”

Section: Discussionmentioning

confidence: 99%

Combination Therapy of Pembrolizumab plus Axitinib for a Patient on Hemodialysis with Metastatic Renal Cell Carcinoma: A Case Report

Kawasaki

Tanaka²,

Nakayama³

et al. 2021

Case Rep Oncol

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Here, we discuss the safety and management of adverse events associated with pembrolizumab plus axitinib combination therapy for metastatic renal cell carcinoma in patients on hemodialysis. A 76-year-old man was diagnosed with cT3aN0M0 renal cell carcinoma due to gross hematuria. Stereoscopic radiotherapy for metastatic lesions of the ipsilateral kidney was performed 9 years after right laparoscopic radical nephrectomy. Soon after, the patient started to receive hemodialysis due to end-stage renal disease. Further stereoscopic radiotherapy was needed for metastasis of the ipsilateral kidney and lung. Fifteen years after diagnosis, systemic therapy was necessary to control new metastases, such as in the right scapular bone. We selected pembrolizumab plus axitinib combination therapy as the first-line systemic therapy for any risk as defined by the International Metastatic RCC Database Consortium. Although we needed to pay attention to the adverse events unique to hemodialysis, he underwent this combination therapy without any difficulty for 6 months. Here, we report the practice of combination therapy in patients on hemodialysis in light of the literature.

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“…The involvement of chronic inflammation, induced by uremic toxins and oxidative stress, 6,7 and impaired immune surveillance, 8,9 has been implicated in the increased incidence 10,11 . As advanced RCCs arising in ESRD respond poorly to systemic therapy such as molecular‐targeted therapy, 12,13 a greater understanding of their pathophysiology is essential.…”

Section: Introductionmentioning

confidence: 99%

Genetic and epigenetic profiling indicates the proximal tubule origin of renal cancers in end‐stage renal disease

Ishihara

Yamashita²,

Liu³

et al. 2020

Cancer Science

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End‐stage renal disease (ESRD) patients on dialysis therapy have a higher incidence of renal cell carcinomas (RCCs), which consist of 2 major histopathological types: clear‐cell RCCs (ESRD‐ccRCCs) and acquired cystic disease (ACD)‐associated RCCs. However, their genetic and epigenetic alterations are still poorly understood. Here, we investigated somatic mutations, copy number alterations (CNAs), and DNA methylation profiles in 9 ESRD‐ccRCCs and 7 ACD‐associated RCCs to identify their molecular alterations and cellular origins. Targeted sequencing of 409 cancer‐related genes, including VHL, PBRM1, SETD2, BAP1, KDM5C, MET, KMT2C (MLL3), and TP53, showed ESRD‐ccRCCs harbored frequent VHL mutations, while ACD‐associated RCCs did not. CNA analysis showed that ESRD‐ccRCCs had a frequent loss of chromosome 3p while ACD‐associated RCCs had a gain of chromosome 16. Beadarray methylation analysis showed that ESRD‐ccRCCs had methylation profiles similar to those of sporadic ccRCCs, while ACD‐associated RCCs had profiles similar to those of papillary RCCs. Expression analysis of genes whose expression levels are characteristic to individual segments of a nephron showed that ESRD‐ccRCCs and ACD‐associated RCCs had high expression of proximal tubule cell marker genes, while chromophobe RCCs had high expression of distal tubule cell/collecting duct cell marker genes. In conclusion, ESRD‐ccRCCs and ACD‐associated RCCs had mutation and methylation profiles similar to those of sporadic ccRCCs and papillary RCCs, respectively, and these 2 histopathological types of RCCs were indicated to have originated from proximal tubule cells of the nephron.

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Efficacy and safety of axitinib for metastatic renal cell carcinoma in patients on hemodialysis for end‐stage renal disease: Case series of eight patients

Cited by 9 publications

References 8 publications

Renal toxicity of targeted therapies for renal cell carcinoma in patients with normal and impaired kidney function

Renal toxicity of targeted therapies for renal cell carcinoma in patients with normal and impaired kidney function

Combination Therapy of Pembrolizumab plus Axitinib for a Patient on Hemodialysis with Metastatic Renal Cell Carcinoma: A Case Report

Genetic and epigenetic profiling indicates the proximal tubule origin of renal cancers in end‐stage renal disease

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