We sought to investigate safety of axitinib or sorafenib in renal cell carcinoma（RCC） patients and compare toxicity of these two vascular endothelial growth factor receptor inhibitors. Databases of PubMed and Embase...We sought to investigate safety of axitinib or sorafenib in renal cell carcinoma（RCC） patients and compare toxicity of these two vascular endothelial growth factor receptor inhibitors. Databases of PubMed and Embase were searched.We included phase II and III prospective trials, as well as retrospective studies, in which patients diagnosed with RCC were treated with axitinib or sorafenib monotherapy at a starting dose of 5 mg and 400 mg twice daily, respectively.The overall incidence of high grade hypertension, fatigue, gastrointestinal toxicity and hand-foot syndrome, along with their 95% confidence intervals（CI）, were calculated using fixed-or random-effects model according to heterogeneity test results. A total of 26 trials, including 4790 patients, were included in our meta-analysis. Among them, 6 arms were related to axitinib and 22 were associated with sorafenib. The incidences of hypertension（24.9%vs. 7.9%）, fatigue（8.2% vs. 6.6%）, and gastrointestinal toxicity（17.6% vs. 11.3%） were higher in patients receiving axitinib versus those receiving sorafenib, while the incidence of hand-foot syndrome was lower in patients receiving axitinib versus those receiving sorafenib（9.5% vs. 13.3%）. In conclusion, axitinib showed noticeably higher risks of toxicity versus sorafenib. Close monitoring and effective measures for adverse events are recommended during therapy.展开更多
BACKGROUND Renal clear cell carcinoma(RCC)is a malignant tumor of the genitourinary system with a predilection for males.The most common metastatic sites are the lung,liver,lymph nodes,contralateral kidney or adrenal ...BACKGROUND Renal clear cell carcinoma(RCC)is a malignant tumor of the genitourinary system with a predilection for males.The most common metastatic sites are the lung,liver,lymph nodes,contralateral kidney or adrenal gland,however,skin metastasis has only been seen in 1.0%-3.3%of cases.The most common site of skin metastasis is the scalp,and metastasis to the nasal ala region is rare.CASE SUMMARY A 55-year-old man with clear cell carcinoma of the left kidney was treated with pembrolizumab and axitinib for half a year after surgery and was found to have a red mass on his right nasal ala for 3 mo.The skin lesion of the patient grew rapidly to the size of 2.0 cm×2.0 cm×1.2 cm after discontinuation of targeted drug therapy due to the coronavirus disease 2019 epidemic.The patient was finally diagnosed with skin metastasis of RCC in our hospital.The patient refused to undergo surgical resection and the tumor shrank rapidly after resuming target therapy for 2 wk.CONCLUSION It is rare for an RCC to metastasize to the skin of the nasal ala region.The tumor size change of this patient before and after treatment with targeted drugs shows the effectiveness of combination therapy for skin metastasis.展开更多
Previous study reported that patients treated with axitinib as second-line therapy had longer median progression-free survival than those treated with sorafenib for metastatic renal cell carcinoma (mRCC). In this stud...Previous study reported that patients treated with axitinib as second-line therapy had longer median progression-free survival than those treated with sorafenib for metastatic renal cell carcinoma (mRCC). In this study, we reviewed our experience of axitinib as a first-line therapy for mRCC in Japanese patients, focusing on its efficacy and safety. We retrospectively assessed 26 patients treated with axitinib as a first-line therapy for mRCC from July 2010 to July 2014 at Chiba Cancer Center and Kinki University Hospital. Observation period was 24.6 ± 18.3 months. The objective response rate was 50.0%, and the median progression-free survival was 27.5 months. Overall survival was not estimable. Common grade 3 adverse events were hypertension in 19 patients and proteinuria in 5 patients. Axitinib demonstrated significant efficacy as a first-line therapy in Japanese patients with mRCC. Careful monitoring and management of the adverse effects may help to control its toxicities.展开更多
In the present study, a simple, rapid, and sensitive liquid chromatography-tandem mass spectrometric method for the determination of axitinib in nude mouse plasma was developed, validated, and applied to a pharmacokin...In the present study, a simple, rapid, and sensitive liquid chromatography-tandem mass spectrometric method for the determination of axitinib in nude mouse plasma was developed, validated, and applied to a pharmacokinetic study. Plasma samples were pre-treated by protein precipitation with acetonitrile spiked with erlotinib as an internal standard. The chromatographic separation was accomplished by using a reversed phase C18 column （50 mm×2 mm, 5 μm） with a simple mobile phase system composed of methanol and water （60：40, v/v） at an isocratic flow rate of 0.4 mL/min. The analyte was detected by a triple-quadrupole tandem mass spectrometer via electrospray ionization and multiple reaction monitoring was employed to select both axitinib and erlotinib in the positive ion mode. The calibration curves were linear （r〉0.99） ranging from 1 to 1000 ng/mL, and the lowest level of this range was the lower limit of quantification. The intra- and inter-day precision were 7.7%-12.0%, and the accuracies ranged from 88.6% to 110.4%. This method was successfully applied to a preclinical pharmacokinetic study on female nu/nu nude mice administrated with a single oral dose of axitinib at 120 mg/kg, and the pharmacokinetics was characterized by a one-compartment model with first-order absorption.展开更多
The therapeutic options for patients with metastatic renal cell carcinoma(mRCC) have completely changed during the last ten years. With the sequential use of targeted therapies, median overall survival has increased i...The therapeutic options for patients with metastatic renal cell carcinoma(mRCC) have completely changed during the last ten years. With the sequential use of targeted therapies, median overall survival has increased in daily practice and now it is not uncommon to see patients surviving kidney cancer for more than four to five years. Once treatment fails with the first line targeted therapy, head to head comparisons have shown that cabozantinib, nivolumab and the combination of lenvatinib plus everolimus are more effective than everolimus alone and that axitinib is more active than sorafenib. Unfortunately, it is very unlikely that we will ever have prospective data comparing the activity of axitinib, cabozantinib, lenvatinib or nivolumab. It is frustrating to observe the lack of biomarkers that we have in this field, thus there is no firm recommendation about the optimal sequence of treatment in the second line. In the absence of reliable biomarkers, there are several clinical endpoints that can help physicians to make decisions for an individual patient, such as the tumor burden, the expected response rate and the time to achieve the response to each agent, the prior response to the agent administered, the toxicity profile of the different compounds and patient preference. Here, we propose the introduction of the tumor-growth rate(TGR) during first-line treatment as a new tool to be used to select the second line strategy in m RCC. The rapidness of TGR before the onset of the treatment reflects the variability between patients in terms of tumor growth kinetics and it could be a surrogate marker of tumor aggressiveness that may guide treatment decisions.展开更多
基金supported by grants from the National Natural Science Foundation of China (81773554 to H. Yu)the National Natural Science Foundation of China Grant for Young Scientists (81302512 to J. Bai)
文摘We sought to investigate safety of axitinib or sorafenib in renal cell carcinoma（RCC） patients and compare toxicity of these two vascular endothelial growth factor receptor inhibitors. Databases of PubMed and Embase were searched.We included phase II and III prospective trials, as well as retrospective studies, in which patients diagnosed with RCC were treated with axitinib or sorafenib monotherapy at a starting dose of 5 mg and 400 mg twice daily, respectively.The overall incidence of high grade hypertension, fatigue, gastrointestinal toxicity and hand-foot syndrome, along with their 95% confidence intervals（CI）, were calculated using fixed-or random-effects model according to heterogeneity test results. A total of 26 trials, including 4790 patients, were included in our meta-analysis. Among them, 6 arms were related to axitinib and 22 were associated with sorafenib. The incidences of hypertension（24.9%vs. 7.9%）, fatigue（8.2% vs. 6.6%）, and gastrointestinal toxicity（17.6% vs. 11.3%） were higher in patients receiving axitinib versus those receiving sorafenib, while the incidence of hand-foot syndrome was lower in patients receiving axitinib versus those receiving sorafenib（9.5% vs. 13.3%）. In conclusion, axitinib showed noticeably higher risks of toxicity versus sorafenib. Close monitoring and effective measures for adverse events are recommended during therapy.
基金Supported by the National Natural Science Foundation of China,No.81803160.
文摘BACKGROUND Renal clear cell carcinoma(RCC)is a malignant tumor of the genitourinary system with a predilection for males.The most common metastatic sites are the lung,liver,lymph nodes,contralateral kidney or adrenal gland,however,skin metastasis has only been seen in 1.0%-3.3%of cases.The most common site of skin metastasis is the scalp,and metastasis to the nasal ala region is rare.CASE SUMMARY A 55-year-old man with clear cell carcinoma of the left kidney was treated with pembrolizumab and axitinib for half a year after surgery and was found to have a red mass on his right nasal ala for 3 mo.The skin lesion of the patient grew rapidly to the size of 2.0 cm×2.0 cm×1.2 cm after discontinuation of targeted drug therapy due to the coronavirus disease 2019 epidemic.The patient was finally diagnosed with skin metastasis of RCC in our hospital.The patient refused to undergo surgical resection and the tumor shrank rapidly after resuming target therapy for 2 wk.CONCLUSION It is rare for an RCC to metastasize to the skin of the nasal ala region.The tumor size change of this patient before and after treatment with targeted drugs shows the effectiveness of combination therapy for skin metastasis.
文摘Previous study reported that patients treated with axitinib as second-line therapy had longer median progression-free survival than those treated with sorafenib for metastatic renal cell carcinoma (mRCC). In this study, we reviewed our experience of axitinib as a first-line therapy for mRCC in Japanese patients, focusing on its efficacy and safety. We retrospectively assessed 26 patients treated with axitinib as a first-line therapy for mRCC from July 2010 to July 2014 at Chiba Cancer Center and Kinki University Hospital. Observation period was 24.6 ± 18.3 months. The objective response rate was 50.0%, and the median progression-free survival was 27.5 months. Overall survival was not estimable. Common grade 3 adverse events were hypertension in 19 patients and proteinuria in 5 patients. Axitinib demonstrated significant efficacy as a first-line therapy in Japanese patients with mRCC. Careful monitoring and management of the adverse effects may help to control its toxicities.
基金National Natural Science Foundation of China(NSFC,Grant No.81473277)
文摘In the present study, a simple, rapid, and sensitive liquid chromatography-tandem mass spectrometric method for the determination of axitinib in nude mouse plasma was developed, validated, and applied to a pharmacokinetic study. Plasma samples were pre-treated by protein precipitation with acetonitrile spiked with erlotinib as an internal standard. The chromatographic separation was accomplished by using a reversed phase C18 column （50 mm×2 mm, 5 μm） with a simple mobile phase system composed of methanol and water （60：40, v/v） at an isocratic flow rate of 0.4 mL/min. The analyte was detected by a triple-quadrupole tandem mass spectrometer via electrospray ionization and multiple reaction monitoring was employed to select both axitinib and erlotinib in the positive ion mode. The calibration curves were linear （r〉0.99） ranging from 1 to 1000 ng/mL, and the lowest level of this range was the lower limit of quantification. The intra- and inter-day precision were 7.7%-12.0%, and the accuracies ranged from 88.6% to 110.4%. This method was successfully applied to a preclinical pharmacokinetic study on female nu/nu nude mice administrated with a single oral dose of axitinib at 120 mg/kg, and the pharmacokinetics was characterized by a one-compartment model with first-order absorption.
文摘The therapeutic options for patients with metastatic renal cell carcinoma(mRCC) have completely changed during the last ten years. With the sequential use of targeted therapies, median overall survival has increased in daily practice and now it is not uncommon to see patients surviving kidney cancer for more than four to five years. Once treatment fails with the first line targeted therapy, head to head comparisons have shown that cabozantinib, nivolumab and the combination of lenvatinib plus everolimus are more effective than everolimus alone and that axitinib is more active than sorafenib. Unfortunately, it is very unlikely that we will ever have prospective data comparing the activity of axitinib, cabozantinib, lenvatinib or nivolumab. It is frustrating to observe the lack of biomarkers that we have in this field, thus there is no firm recommendation about the optimal sequence of treatment in the second line. In the absence of reliable biomarkers, there are several clinical endpoints that can help physicians to make decisions for an individual patient, such as the tumor burden, the expected response rate and the time to achieve the response to each agent, the prior response to the agent administered, the toxicity profile of the different compounds and patient preference. Here, we propose the introduction of the tumor-growth rate(TGR) during first-line treatment as a new tool to be used to select the second line strategy in m RCC. The rapidness of TGR before the onset of the treatment reflects the variability between patients in terms of tumor growth kinetics and it could be a surrogate marker of tumor aggressiveness that may guide treatment decisions.
