BACKGROUND Sunitinib,a multi-targeted tyrosine kinase inhibitor(TKI),has been approved for the salvage treatment of gastrointestinal stromal tumors(GIST).Hyperammonemic encephalopathy is a rare but severe complication...BACKGROUND Sunitinib,a multi-targeted tyrosine kinase inhibitor(TKI),has been approved for the salvage treatment of gastrointestinal stromal tumors(GIST).Hyperammonemic encephalopathy is a rare but severe complication of sunitinib use.Here,we present the case of a 66-year-old male with metastatic GIST without underlying liver cirrhosis who developed sunitinib-induced hyperammonemic encephalopathy.CASE SUMMARY A 66-year-old male with metastatic GIST was admitted because of reduced consciousness.Imatinib was administered as the first-line systemic therapy.He experienced repeated episodes of peritonitis due to tumor perforation,and surgery was performed.Progressive disease was confirmed based on increased liver metastasis,and sunitinib was initiated as a salvage treatment.However,23 d after the third course of sunitinib,he presented to the emergency room with an episode of altered consciousness and behavioral changes.Based on the patient clinical history and examination findings,sunitinib-induced encephalopathy was suspected.Sunitinib was discontinued,and the patient was treated for hyperammonemia.The patient had a normal level of consciousness four days later,and the serum ammonia level gradually decreased.No further neurological symptoms were reported in subsequent follow-ups.CONCLUSION TKI-induced hyperammonemic encephalopathy is potentially life-threatening.Patients receiving TKIs experiencing adverse reactions should undergo systemic evaluation and prompt treatment.展开更多
Background: Sorafenib and sunitinib are widely used as first-line targeted therapy for metastatic renal cell carcinoma(mRCC) in China.This study aimed to compare the efficacy, safety, and quality of life(QoL) in Chine...Background: Sorafenib and sunitinib are widely used as first-line targeted therapy for metastatic renal cell carcinoma(mRCC) in China.This study aimed to compare the efficacy, safety, and quality of life(QoL) in Chinese mRCC patients treated with sorafenib and sunitinib as first-line therapy.Methods: Clinical data of patients with mRCC who received sorafenib(400 mg twice daily; 4 weeks) or sunitinib(50 mg twice daily; on a schedule of 4 weeks on treatment followed by 2 weeks off) were retrieved. Primary outcomes were overall survival(OS), progression-free survival(PFS), adverse events(AEs), and QoL(SF-36 scores), and secondary outcomes were associations of clinical characteristics with QoL.Results: Medical records of 184 patients(110 in the sorafenib group and 74 in the sunitinib group) were reviewed.PFS and OS were comparable between the sorafenib and sunitinib groups(both P > 0.05).The occurrence rates of leukocytopenia, thrombocytopenia, and hypothyroidism were higher in the sunitinib group(36.5% vs. 10.9%,P< 0.001; 40.5% vs. 10.9%, P < 0.001; 17.6% vs. 3.6%, P = 0.001), and that of diarrhea was higher in the sorafenib group(62.7% vs. 35.2%, P < 0.001). There was no significant difference in SF-36 scores between the two groups. Multivariate analysis indicated that role-physical and bodily pain scores were associated with the occurrence rate of grade 3 or 4 AEs(P = 0.017 and 0.005).Conclusions: Sorafenib has comparable efficacy and lower toxicity profile than sunitinib as first-line therapy for mRCC. Both agents showed no significant impact on QoL of patients.展开更多
Gastrointestinal stromal tumor （GIST） represents the most common mesenchymal malignancy of the gastrointestinal （GI） tract. In neurofibromatosis （NF）, the increased incidence of tumor needs to be considered even...Gastrointestinal stromal tumor （GIST） represents the most common mesenchymal malignancy of the gastrointestinal （GI） tract. In neurofibromatosis （NF）, the increased incidence of tumor needs to be considered even in non-symptomatic individuals. Patients with neurofibromatosis NF type 1 have an increased risk of developing GI tumors including rare types such as GIST. We report a case of GIST in a 53-year-old male patient with neurofibromatosis. The patient was diagnosed with NF four years ago and his medical history revealed that he was hospitalized 5 times with a provisional diagnosis of massive lower gastrointestinal bleeding. GIST was diagnosed at explorative laparotomy and the tumor was 21 cm × 13 cm × 7 cm in size. Immunohistochemical examination showed that vimentin, actin and CDl17 were positive. Computerized tomography showed peritoneal implants three months later. Imatinib mesylate （600 mg/d） was initiated. However, control computerized tomography revealed liver and omental metastasis. The dosage was elevated to 800 mg/d. Despite high dosage, the progression of the metastatic lesions continued in the liver and omentum. The patient started oral sunitinib malate （Sutent~ Pfizer Inc, New York, NY, USA） 50 mg per day for 4 consecutive weeks, followed by 2 wk off per treatment cycle. The metastatic lesions in the liver and omentum were decreased in size after four courses, suggesting that sunitinib is also an effective treatment modality for metastatic GIST in NF patients.展开更多
The molecular targets of sunitinib are receptor tyrosine kinases (RTKs),and this drug has also been known to exert blocking effects on the activation of KIT,which is similar to the mechanism of action of imatinib. Mor...The molecular targets of sunitinib are receptor tyrosine kinases (RTKs),and this drug has also been known to exert blocking effects on the activation of KIT,which is similar to the mechanism of action of imatinib. Moreover,sunitinib has an additional anti-angiogenic effect through its inhibition of the vascular endothelial growth factor receptor activation. We report here a 70-year-old patient diagnosed with a recurrent gastrointestinal stromal tumor (GIST),which invaded the transverse colon and led to a perforation during sunitinib treatment. A computed tomography scan and 3-dimensional reconstruction showed necrosis of the recurrent hepatic mass and perforation of the invaded transverse colon. After percutaneous drainage of the intraperitoneal abscess,antibiotic treatment and restricted diet,the condition of the patient improved. The present case is the first to report that sunitinib,which is administered to treat GIST resistant to imatinib,can cause unexpected colon perforation and subsequent peritonitis.展开更多
AIM: To study if three clinically available small molecule kinase inhibitors (SMI), erlotinib, sunitinib and sorafenib, exert antifibrogenic effects on pancreatic stellate cells (PSC) and analyze the basis of their ac...AIM: To study if three clinically available small molecule kinase inhibitors (SMI), erlotinib, sunitinib and sorafenib, exert antifibrogenic effects on pancreatic stellate cells (PSC) and analyze the basis of their action.展开更多
Objective To investigate the growth-inhibitory effect of sunitinib malate on human bladder transitional cell carcinoma （TCC） in vitro. Methods Human bladder TCC cell line T24 was cultured and exposed to graded conc...Objective To investigate the growth-inhibitory effect of sunitinib malate on human bladder transitional cell carcinoma （TCC） in vitro. Methods Human bladder TCC cell line T24 was cultured and exposed to graded concentrations of sunitinib malate for 72 hours in vitro to determine the sensitivities to drug. Cell viability was measured by MTT assay. Cell apoptotic morphology was observed by fluorescence microscope following DAPl staining. Band expressions of Fas, Fas ligand, poly （ADP-ribose） polyrnerase （PARP） and D-actin were analyzed by Western blot. Wound healing process of T24 cells exposed to sunitinib malate was assayed. Results Sunitinib malate exerted a concentration-dependent and time-dependent inhibitory effect on the T24 cell lines. Fluorescence microscopy showed that small vacuoles appeared in the nuclei of T24 cells and the vacuoles were bigger with higher drug concentrations. The expressions of Fas ligand and PARP in T24 cells treated with sunitinib malate exhibited a concentration-dependent increase. Moreover sunitinib malate suppressed the wound healing process in a concentration-dependent manner. Conclusion Sunitinib malate exerted marked inhibitory activity against bladder cancer cell line T24.展开更多
Sunitinib malate is one of the multitargeted tyrosine kinase inhibitor,which are being used in clinic.It can inhibit more than 80 kinds of receptor`s tyrosine kinase,including epidermal growth factor receptor (EGFR),p...Sunitinib malate is one of the multitargeted tyrosine kinase inhibitor,which are being used in clinic.It can inhibit more than 80 kinds of receptor`s tyrosine kinase,including epidermal growth factor receptor (EGFR),platelet-derived growth factor receptors,vascular endothelial growth factor receptors (VEGFR),etc.And tyrosine kinase inhibitor is involved in connection with the generation and progression of many kinds of cancer including lung cancer.Several studies have evaluated the effect of Sunitinib on non-small cell lung cancer (NSCLC),by single agent,continuous daily dosing or in combination with chemotherapeutics (with docetaxel or gemcitabine plus cisplatin),which all showed certain effect.The test of Sunitinib in combination with gemcitabine plus cisplatin for advanced NSCLC shown that at the maximum tolerated dose:oral Sunitinib 37.5 mg/day intermittently (Schedule 2/1:2 weeks on treatment,1 week off treatment) schedule with intravenous infusions of gemcitabine (1000 mg/m2 days 1,8) and cisplatin (80 mg/m2 day 1),administered in 3-week cycles,66.7% patients achieved partial responses.And adverse effects were mild to moderate in severity (grades 1 to 2).Therapy was generally well tolerated.In summary,all the evidence above suggests that Sunitinib may play an important role in the treating of NSCLC.展开更多
Background: Anaplastic thyroid cancer (ATC), while rare, carries a uniformly poor prognosis. Current treatment includes surgery when possible, radiotherapy, and chemotherapy. Multiple chemotherapeutic agents are in th...Background: Anaplastic thyroid cancer (ATC), while rare, carries a uniformly poor prognosis. Current treatment includes surgery when possible, radiotherapy, and chemotherapy. Multiple chemotherapeutic agents are in the process of clinical testing, and promising agents include those in the tyrosine kinase inhibitor family. Our patient represents a novel case of ATC treated with sunitinib, one such tyrosine kinase inhibitor. Methods/Results: We utilized the experimental sunitinib in conjunction with radiation therapy to treat a patient with aggressive ATC in whom curative resection was unable to be achieved due to carotid sheath and tracheal involvement. The patient had marked clinical response and sustained stable disease for 8 months, which coincides with reported data regarding sunitinib to treat other thyroid malignancies. Conclusion: Our case illustrates the efficacy of sunitinib therapy as a possible adjunct in the treatment of ATC.展开更多
Objective: This study aim to assess the efficacy and safety of sunitinib in Japanese patients with metastatic renal cell carcinoma (mRCC) in general clinical practice. Patients and Methods: Non-selected fifty eight Ja...Objective: This study aim to assess the efficacy and safety of sunitinib in Japanese patients with metastatic renal cell carcinoma (mRCC) in general clinical practice. Patients and Methods: Non-selected fifty eight Japanese patients with mRCC were treated with sunitinib. Overall survival (OS) and time to treatment failure (TTF) were estimated. Response rate and safety profiles were also assessed. Results: Partial response, stable disease, and progressive disease were observed in 13 (22.4%), 26 (44.8%), and 19 (32.8%) patients, respectively. The median TTF was 5.4 months, and the median OS was 11.2 months. In the prior nephrectomy group, the median TTF was 9.0 months, and the median OS was 16.4 months. In the non-nephrectomy group, the median TTF was 1.1 months, and the median OS was 2.8 months. The most frequently occurring Grade 3/4 adverse events (AEs) were anorexia (17.2%), fatigue (12.1%), thrombocytopenia (13.8%), and anemia (12.1%). Conclusions: Sunitinib has a favorable risk/benefit profile in Japanese mRCC patients with a history of nephrectomy.展开更多
The authors herein report the case of a 67-year-old woman with metastatic renal-cell carcinoma (RCC), who has had a sustained clinical and stable radiological response to long-term therapy with an oral multi-targeted ...The authors herein report the case of a 67-year-old woman with metastatic renal-cell carcinoma (RCC), who has had a sustained clinical and stable radiological response to long-term therapy with an oral multi-targeted tyrosine kinase inhibitor (TKI), sunitinib with minimal lasting toxicity.展开更多
Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia, is a skin toxicity that could be observed during target therapies such as with tyrosine-kinase inhibitors (TKI). It usually develops within th...Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia, is a skin toxicity that could be observed during target therapies such as with tyrosine-kinase inhibitors (TKI). It usually develops within the first 2 - 4 weeks of drug administration. We present a case of HFS induced by Pazopanib after 2 months of treatment, in patients previously treated with Sunitinib, suggesting a possible cumulative toxicity of two drugs. The clinical and therapeutic management of skin adverse reactions during TKI therapy usually requires 25% dose reduction and adequate local treatment. It is important for the clinicians to recognize clinical signs and symptoms of such skin toxicities. Attention should be paid especially when two or more drugs from the same class are used in combined treatment.展开更多
Sunitinib is an orally administered, multi-target tyrosine kinase inhibitor that has been approved by the FDA for the treatment of renal cell carcinoma and imatinib resistant gastro-intestinal tumors. Anti-leukemic ac...Sunitinib is an orally administered, multi-target tyrosine kinase inhibitor that has been approved by the FDA for the treatment of renal cell carcinoma and imatinib resistant gastro-intestinal tumors. Anti-leukemic activity of sunitinib has been examined in early clinical trials with limited success. However, recent trials on acute myeloid leukemia (AML) patients carrying FLT3 mutations have shown promising results. Effects of sunitinib on leukemic clonogenic cells and potential leukemic stem cells have not been examined so far. We analyzed the anti-proliferative and apoptotic properties of sunitinib on AML-derived cell lines. We also tested the effect of sunitinib on AML patient derived clonogenic cells (AML-CFC), as well as flow-sorted potential leukemic progenitors. Peripheral blood or bone marrow samples were obtained from newly diagnosed AML patients and flow sorted for CD34+ CD133+ or ALDH+ cells. Umbilical cord blood derived CD34+ cells were used as normal controls. Sunitinib induced growth arrest and apoptosis in AML derived cell lines. In addition, 7 μM sunitinib induced 75% reduction of AML-CFC as compared to DMSO treated control (±6.79%;n = 4). In contrast, 7 μM sunitinib treatment of umbilical cord blood derived normal CD34+ cells showed 29% reduction in AML-CFC (±6.77%;n = 5). Treatment of ALDH+ cells sorted from 2 AML cases and CD34+ CD133+ cells from one patient showed reduction of AML-CFC on treatment with sunitinib. Our study highlighted a potent anti-proliferative and proapoptotic effect of sunitinib on AML cell lines, AML patient derived clonogenic cells and potential leukemic stem cells.展开更多
Objective:To study the effect of sunitinib on renal cancer cell growth and invasion in vitro as well as Wnt/β-catenin signaling pathway.Methods: Renal cancer cell lines ACHN were cultured and processed with different...Objective:To study the effect of sunitinib on renal cancer cell growth and invasion in vitro as well as Wnt/β-catenin signaling pathway.Methods: Renal cancer cell lines ACHN were cultured and processed with different doses of sunitinib (1 μmol/L, 2 μmol/L, 4 μmol/L and 8 μmol/L), and sunitinib-free processing condition was used as negative control. 24 h after processing, the mRNA expression levels of apoptosis genes, invasion genes and Wnt/β-catenin signaling pathways in cells were detected.Results: 24 h after treatment, NPRL2, Bax, caspase-3 and caspase-9 mRNA expression in 1 μmol/L, 2 μmol/L, 4 μmol/L and 8 μmol/L sunitinib groups were significantly higher than those in negative control group while MMP2, MMP9, Vimentin, N-cadherin, Wnt andβ-catenin mRNA expression were significantly lower than those in negative control group;the higher the dose of sunitinib, the higher the NPRL2, Bax, caspase-3 and caspase-9 mRNA expression while the lower the MMP2, MMP9, Vimentin, N-cadherin, Wnt andβ-catenin mRNA expression in cells.Conclusion: Sunitinib can inhibit the Wnt/β-catenin signaling pathway in renal cancer cells to increase the expression of apoptosis genes, inhibit the expression of invasion genes and thereby inhibit the cell growth and invasion.展开更多
Objective To evaluate the clinical efficacy and side effects of sunitinib in treatment of advanced renal cell carcinoma. Methods Forty-five patients with advanced renal cell carcinorna and an average age of 48. 6 yrs ...Objective To evaluate the clinical efficacy and side effects of sunitinib in treatment of advanced renal cell carcinoma. Methods Forty-five patients with advanced renal cell carcinorna and an average age of 48. 6 yrs were treated with sunitinib. of the study group。展开更多
文摘BACKGROUND Sunitinib,a multi-targeted tyrosine kinase inhibitor(TKI),has been approved for the salvage treatment of gastrointestinal stromal tumors(GIST).Hyperammonemic encephalopathy is a rare but severe complication of sunitinib use.Here,we present the case of a 66-year-old male with metastatic GIST without underlying liver cirrhosis who developed sunitinib-induced hyperammonemic encephalopathy.CASE SUMMARY A 66-year-old male with metastatic GIST was admitted because of reduced consciousness.Imatinib was administered as the first-line systemic therapy.He experienced repeated episodes of peritonitis due to tumor perforation,and surgery was performed.Progressive disease was confirmed based on increased liver metastasis,and sunitinib was initiated as a salvage treatment.However,23 d after the third course of sunitinib,he presented to the emergency room with an episode of altered consciousness and behavioral changes.Based on the patient clinical history and examination findings,sunitinib-induced encephalopathy was suspected.Sunitinib was discontinued,and the patient was treated for hyperammonemia.The patient had a normal level of consciousness four days later,and the serum ammonia level gradually decreased.No further neurological symptoms were reported in subsequent follow-ups.CONCLUSION TKI-induced hyperammonemic encephalopathy is potentially life-threatening.Patients receiving TKIs experiencing adverse reactions should undergo systemic evaluation and prompt treatment.
基金supported by the National Natural Science Foundation of China(Nos.81402084,81472378)the Shanghai Municipal Commission of Health and Family Planning(No.2013SY027)the Incubating Program for Clinical Research and Innovation of Renji Hospital(No.PYXJS16-008)
文摘Background: Sorafenib and sunitinib are widely used as first-line targeted therapy for metastatic renal cell carcinoma(mRCC) in China.This study aimed to compare the efficacy, safety, and quality of life(QoL) in Chinese mRCC patients treated with sorafenib and sunitinib as first-line therapy.Methods: Clinical data of patients with mRCC who received sorafenib(400 mg twice daily; 4 weeks) or sunitinib(50 mg twice daily; on a schedule of 4 weeks on treatment followed by 2 weeks off) were retrieved. Primary outcomes were overall survival(OS), progression-free survival(PFS), adverse events(AEs), and QoL(SF-36 scores), and secondary outcomes were associations of clinical characteristics with QoL.Results: Medical records of 184 patients(110 in the sorafenib group and 74 in the sunitinib group) were reviewed.PFS and OS were comparable between the sorafenib and sunitinib groups(both P > 0.05).The occurrence rates of leukocytopenia, thrombocytopenia, and hypothyroidism were higher in the sunitinib group(36.5% vs. 10.9%,P< 0.001; 40.5% vs. 10.9%, P < 0.001; 17.6% vs. 3.6%, P = 0.001), and that of diarrhea was higher in the sorafenib group(62.7% vs. 35.2%, P < 0.001). There was no significant difference in SF-36 scores between the two groups. Multivariate analysis indicated that role-physical and bodily pain scores were associated with the occurrence rate of grade 3 or 4 AEs(P = 0.017 and 0.005).Conclusions: Sorafenib has comparable efficacy and lower toxicity profile than sunitinib as first-line therapy for mRCC. Both agents showed no significant impact on QoL of patients.
文摘Gastrointestinal stromal tumor （GIST） represents the most common mesenchymal malignancy of the gastrointestinal （GI） tract. In neurofibromatosis （NF）, the increased incidence of tumor needs to be considered even in non-symptomatic individuals. Patients with neurofibromatosis NF type 1 have an increased risk of developing GI tumors including rare types such as GIST. We report a case of GIST in a 53-year-old male patient with neurofibromatosis. The patient was diagnosed with NF four years ago and his medical history revealed that he was hospitalized 5 times with a provisional diagnosis of massive lower gastrointestinal bleeding. GIST was diagnosed at explorative laparotomy and the tumor was 21 cm × 13 cm × 7 cm in size. Immunohistochemical examination showed that vimentin, actin and CDl17 were positive. Computerized tomography showed peritoneal implants three months later. Imatinib mesylate （600 mg/d） was initiated. However, control computerized tomography revealed liver and omental metastasis. The dosage was elevated to 800 mg/d. Despite high dosage, the progression of the metastatic lesions continued in the liver and omentum. The patient started oral sunitinib malate （Sutent~ Pfizer Inc, New York, NY, USA） 50 mg per day for 4 consecutive weeks, followed by 2 wk off per treatment cycle. The metastatic lesions in the liver and omentum were decreased in size after four courses, suggesting that sunitinib is also an effective treatment modality for metastatic GIST in NF patients.
文摘The molecular targets of sunitinib are receptor tyrosine kinases (RTKs),and this drug has also been known to exert blocking effects on the activation of KIT,which is similar to the mechanism of action of imatinib. Moreover,sunitinib has an additional anti-angiogenic effect through its inhibition of the vascular endothelial growth factor receptor activation. We report here a 70-year-old patient diagnosed with a recurrent gastrointestinal stromal tumor (GIST),which invaded the transverse colon and led to a perforation during sunitinib treatment. A computed tomography scan and 3-dimensional reconstruction showed necrosis of the recurrent hepatic mass and perforation of the invaded transverse colon. After percutaneous drainage of the intraperitoneal abscess,antibiotic treatment and restricted diet,the condition of the patient improved. The present case is the first to report that sunitinib,which is administered to treat GIST resistant to imatinib,can cause unexpected colon perforation and subsequent peritonitis.
基金Supported by Grant from the Deutsche Forschungsgemeinschaft(to RJ)
文摘AIM: To study if three clinically available small molecule kinase inhibitors (SMI), erlotinib, sunitinib and sorafenib, exert antifibrogenic effects on pancreatic stellate cells (PSC) and analyze the basis of their action.
基金Supported by the Beijing Natural Science Foundation(7102128)
文摘Objective To investigate the growth-inhibitory effect of sunitinib malate on human bladder transitional cell carcinoma （TCC） in vitro. Methods Human bladder TCC cell line T24 was cultured and exposed to graded concentrations of sunitinib malate for 72 hours in vitro to determine the sensitivities to drug. Cell viability was measured by MTT assay. Cell apoptotic morphology was observed by fluorescence microscope following DAPl staining. Band expressions of Fas, Fas ligand, poly （ADP-ribose） polyrnerase （PARP） and D-actin were analyzed by Western blot. Wound healing process of T24 cells exposed to sunitinib malate was assayed. Results Sunitinib malate exerted a concentration-dependent and time-dependent inhibitory effect on the T24 cell lines. Fluorescence microscopy showed that small vacuoles appeared in the nuclei of T24 cells and the vacuoles were bigger with higher drug concentrations. The expressions of Fas ligand and PARP in T24 cells treated with sunitinib malate exhibited a concentration-dependent increase. Moreover sunitinib malate suppressed the wound healing process in a concentration-dependent manner. Conclusion Sunitinib malate exerted marked inhibitory activity against bladder cancer cell line T24.
文摘Sunitinib malate is one of the multitargeted tyrosine kinase inhibitor,which are being used in clinic.It can inhibit more than 80 kinds of receptor`s tyrosine kinase,including epidermal growth factor receptor (EGFR),platelet-derived growth factor receptors,vascular endothelial growth factor receptors (VEGFR),etc.And tyrosine kinase inhibitor is involved in connection with the generation and progression of many kinds of cancer including lung cancer.Several studies have evaluated the effect of Sunitinib on non-small cell lung cancer (NSCLC),by single agent,continuous daily dosing or in combination with chemotherapeutics (with docetaxel or gemcitabine plus cisplatin),which all showed certain effect.The test of Sunitinib in combination with gemcitabine plus cisplatin for advanced NSCLC shown that at the maximum tolerated dose:oral Sunitinib 37.5 mg/day intermittently (Schedule 2/1:2 weeks on treatment,1 week off treatment) schedule with intravenous infusions of gemcitabine (1000 mg/m2 days 1,8) and cisplatin (80 mg/m2 day 1),administered in 3-week cycles,66.7% patients achieved partial responses.And adverse effects were mild to moderate in severity (grades 1 to 2).Therapy was generally well tolerated.In summary,all the evidence above suggests that Sunitinib may play an important role in the treating of NSCLC.
文摘Background: Anaplastic thyroid cancer (ATC), while rare, carries a uniformly poor prognosis. Current treatment includes surgery when possible, radiotherapy, and chemotherapy. Multiple chemotherapeutic agents are in the process of clinical testing, and promising agents include those in the tyrosine kinase inhibitor family. Our patient represents a novel case of ATC treated with sunitinib, one such tyrosine kinase inhibitor. Methods/Results: We utilized the experimental sunitinib in conjunction with radiation therapy to treat a patient with aggressive ATC in whom curative resection was unable to be achieved due to carotid sheath and tracheal involvement. The patient had marked clinical response and sustained stable disease for 8 months, which coincides with reported data regarding sunitinib to treat other thyroid malignancies. Conclusion: Our case illustrates the efficacy of sunitinib therapy as a possible adjunct in the treatment of ATC.
文摘Objective: This study aim to assess the efficacy and safety of sunitinib in Japanese patients with metastatic renal cell carcinoma (mRCC) in general clinical practice. Patients and Methods: Non-selected fifty eight Japanese patients with mRCC were treated with sunitinib. Overall survival (OS) and time to treatment failure (TTF) were estimated. Response rate and safety profiles were also assessed. Results: Partial response, stable disease, and progressive disease were observed in 13 (22.4%), 26 (44.8%), and 19 (32.8%) patients, respectively. The median TTF was 5.4 months, and the median OS was 11.2 months. In the prior nephrectomy group, the median TTF was 9.0 months, and the median OS was 16.4 months. In the non-nephrectomy group, the median TTF was 1.1 months, and the median OS was 2.8 months. The most frequently occurring Grade 3/4 adverse events (AEs) were anorexia (17.2%), fatigue (12.1%), thrombocytopenia (13.8%), and anemia (12.1%). Conclusions: Sunitinib has a favorable risk/benefit profile in Japanese mRCC patients with a history of nephrectomy.
文摘The authors herein report the case of a 67-year-old woman with metastatic renal-cell carcinoma (RCC), who has had a sustained clinical and stable radiological response to long-term therapy with an oral multi-targeted tyrosine kinase inhibitor (TKI), sunitinib with minimal lasting toxicity.
文摘Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia, is a skin toxicity that could be observed during target therapies such as with tyrosine-kinase inhibitors (TKI). It usually develops within the first 2 - 4 weeks of drug administration. We present a case of HFS induced by Pazopanib after 2 months of treatment, in patients previously treated with Sunitinib, suggesting a possible cumulative toxicity of two drugs. The clinical and therapeutic management of skin adverse reactions during TKI therapy usually requires 25% dose reduction and adequate local treatment. It is important for the clinicians to recognize clinical signs and symptoms of such skin toxicities. Attention should be paid especially when two or more drugs from the same class are used in combined treatment.
文摘Sunitinib is an orally administered, multi-target tyrosine kinase inhibitor that has been approved by the FDA for the treatment of renal cell carcinoma and imatinib resistant gastro-intestinal tumors. Anti-leukemic activity of sunitinib has been examined in early clinical trials with limited success. However, recent trials on acute myeloid leukemia (AML) patients carrying FLT3 mutations have shown promising results. Effects of sunitinib on leukemic clonogenic cells and potential leukemic stem cells have not been examined so far. We analyzed the anti-proliferative and apoptotic properties of sunitinib on AML-derived cell lines. We also tested the effect of sunitinib on AML patient derived clonogenic cells (AML-CFC), as well as flow-sorted potential leukemic progenitors. Peripheral blood or bone marrow samples were obtained from newly diagnosed AML patients and flow sorted for CD34+ CD133+ or ALDH+ cells. Umbilical cord blood derived CD34+ cells were used as normal controls. Sunitinib induced growth arrest and apoptosis in AML derived cell lines. In addition, 7 μM sunitinib induced 75% reduction of AML-CFC as compared to DMSO treated control (±6.79%;n = 4). In contrast, 7 μM sunitinib treatment of umbilical cord blood derived normal CD34+ cells showed 29% reduction in AML-CFC (±6.77%;n = 5). Treatment of ALDH+ cells sorted from 2 AML cases and CD34+ CD133+ cells from one patient showed reduction of AML-CFC on treatment with sunitinib. Our study highlighted a potent anti-proliferative and proapoptotic effect of sunitinib on AML cell lines, AML patient derived clonogenic cells and potential leukemic stem cells.
文摘Objective:To study the effect of sunitinib on renal cancer cell growth and invasion in vitro as well as Wnt/β-catenin signaling pathway.Methods: Renal cancer cell lines ACHN were cultured and processed with different doses of sunitinib (1 μmol/L, 2 μmol/L, 4 μmol/L and 8 μmol/L), and sunitinib-free processing condition was used as negative control. 24 h after processing, the mRNA expression levels of apoptosis genes, invasion genes and Wnt/β-catenin signaling pathways in cells were detected.Results: 24 h after treatment, NPRL2, Bax, caspase-3 and caspase-9 mRNA expression in 1 μmol/L, 2 μmol/L, 4 μmol/L and 8 μmol/L sunitinib groups were significantly higher than those in negative control group while MMP2, MMP9, Vimentin, N-cadherin, Wnt andβ-catenin mRNA expression were significantly lower than those in negative control group;the higher the dose of sunitinib, the higher the NPRL2, Bax, caspase-3 and caspase-9 mRNA expression while the lower the MMP2, MMP9, Vimentin, N-cadherin, Wnt andβ-catenin mRNA expression in cells.Conclusion: Sunitinib can inhibit the Wnt/β-catenin signaling pathway in renal cancer cells to increase the expression of apoptosis genes, inhibit the expression of invasion genes and thereby inhibit the cell growth and invasion.
文摘Objective To evaluate the clinical efficacy and side effects of sunitinib in treatment of advanced renal cell carcinoma. Methods Forty-five patients with advanced renal cell carcinorna and an average age of 48. 6 yrs were treated with sunitinib. of the study group。
